Sunday, 24 June 2018


One more evidence

DKFZ The German Cancer Research Center is Germany's largest biomedical research institute with a thousand scientists. On 20th June 2018 they reported a discovery in the field of aging. I will quote some of what they report: 'Oxidative stress causes cells and entire organisms to age. If reactive oxygen species accumulate, this causes damage to the DNA as well as changes in the protein molecules and lipids in the cell. The cell ultimately loses its functionality and dies. Over time, the tissue suffers and the body ages. "The theory of oxidative stress or the accumulation of reactive oxygen species as the cause of aging has existed since the 1950s," says Peter Krammer of the German Cancer Research Center (DKFZ). "So far, however, the details of this process were unclear."
One way in which the body disposes of harmful reactive oxygen species is their conversion by the enzyme thioredoxin-1 (TRX-1). TRX-1 has been proven to play a role in protecting DNA from oxidative stress and slowing down aging processes. Its antagonist TXNIP inhibits thioredoxin-1 and thus ensures that the reactive oxygen molecules are retained.
In fact, reactive oxygen species (ROS) do more than just damage the body. For example, they are essential for the T-cells of the immune system to become active.' So ROS is also beneficial in the right proportion. The key is for excess ROS to be processed away before it can become harmful. But inversely, too much TRX-1 can impair critical immune related activity triggered by ROS. As I have stated in my earlier blog post called 'Mechanism of Aging' Nature modulates levels by using agonist and antagonists. It's like a hot water tap and a cold water tap and one can adjust their output to get water at just the right temperature. Where water represents repair pathway. Excess of either cold or hot can make it painful and harmful for us. Just the right temperature is called homeostatic state in our biology. 
When we are young the agonists Trx1 and antagonists TXNIP maintain just the right levels of ROS. But as per theory proposed in my earlier post ' Mechanism of Aging' Nature selectively increases the levels of antagonists as we age in a progressive manner. This begins to progressively increase the levels of ROS. To continue with my comparitive example it's like cold water is drowned out by increasing levels of hot water. At one point it begins to scald. That is what happens with uncontrolled ROS damaging for example DNA to a scale at which DNA's repair enzymes can't keep up. Nature by the way also modulates DNA repair systems with agonist and antagonist molecules. DNA repair is activated by PARP1 whose antagonist is DBC1 and agonist is NAD+. So can you see a pattern emerging here? TXNIP domination over TRX-1 as we age leads to rising ROS levels. One of the damage excessive ROS causes is to DNA. But as we age and just when DNA needs it most DBC1 levels also begins to dominate over NAD+ levels. So ROS causes more DNA damage just when less and less repair enzymes are available to repair it. Mounting unrepaired DNA damage then leads to rising mutations and genomic instability. 
I am excited by the DKFZ findings as it corroborates the theory proposed in mechanism of aging post on this blog of how aging program is implemented in our body. What you read above is happening in all major repair pathways and it snowballs progressively making death unavoidable. But what would happen if we selectively upregulate the dwindling agonists of repair? In the case of upregulation of NAD+ David Sinclair's lab at Harvard Medical School showed that DNA repair markers improved. Similarly the DKFZ researchers led by Krammer and Gülow wanted to know whether more TXNIP is formed in the body with increasing age, thereby undermining the protective mechanism against oxidative stress. To this end, they first compared T cells from the blood of a group of over 55-year-old volunteers with the T cells of younger blood donors, who were between 20 and 25 years old. In fact, it turned out that the cells of older subjects produce significantly more TXNIP. The DKFZ scientists have also observed similar findings in other human cell and tissue types. They also found TXNIP levels similarly much higher in older flies. Upregulation of TRX-1 would balance out the higher levels of TXNIP thereby forestalling the damaging chain reaction of rising ROS levels.
Another Evidence:
Autophagy is a very important repair and recycling pathway. With aging this too progressively goes down in efficiency leaving more and more senescent cells. It's importance can be gauged by the $307 million raised by Unity Bio based on pre-clinical data about a molecule that can clear senescent cells. One of their investors is now the world's wealthiest man Jeff Bezos founder of Amazon.
As cells die autophagy recycles the dead cells into new cells and clears debris. If this doesn't happen efficiently, aging humans are left with dead zombie cells (senescent cells) that secrete damaging cytokines harming surrounding healthy cells leading to mounting damage in tissues and organs.
Alvaro Fernandez and Salwa Sebti along with colleagues at University of Texas Southwestern Medical Center, USA published a study in Nature Journal on 30th May 2018. As per theory of mechanism of aging posted on this blog there is negative regulator of autophagy - antagonist called BCL2. It interacts with Beclin 1 a regulator of autophagy and apoptosis and blocks autophagy. As we age guess what happens. BCL2 increases it's interaction with Beclin 1. When the scientists disrupted this interaction between them it increased autophagy. Just bringing up one major repair and recycling pathway back to youthful levels not only increased healthspan but also lifespan. 
Now as promised I am sharing very good news for all who wished us luck for our pre-clinical trials mentioned in the post Mechanism of Aging: We have the results of a 2 month study where we selectively administered natural molecules and compounds that upregulate major known repair pathways. First of all safety tests cleared with flying colors histopathologist could not distinguish between young and treated old tissues. The main trial results were also spectacular: chronic inflammation of treated old rats reversed all the way back to levels of young control rats! Muscle strength - grip strength of old treated rats went up almost reaching young control rats! And cognitive skills - memory test scores of old treated rats were close to young control rats! The old treated rats lost weight despite having same amount of feed as old untreated rats! There was a wide difference between the levels of old treated rats and old untreated rats. If these are some of the key markers of aging did we reverse the age of old treated rats back to youth? It was equivalent of a 70 year old developing the metabolism, strength and memory of a 20 year old. Does it prove the theory of how Nature implements it's aging program? The anti aging benefit derived by rapamycin and metformin are limited and triggered only in a narrow range as it is a hormetic intervention. Anti aging benefits derived by resettng gene expression which has been methylated by aging changes to the epigenome theoretically may not be restricted by a narrow bandwidth. We have to find out over hundreds of studies whether this can be the fountain of youth we have been searching from thousands of years. Now on to human clinical trials. Please wish us luck.

Friday, 1 December 2017


Hormesis is evolutionarily conserved stress response. No other anti aging therapy has shown beneficial results in humans so far except Hormetic interventions like Calorie Restriction, prolonged fasting, intermittent low dose rapamycin and metformin. 
We come across all kinds of stress on a daily basis like UV radiation, very hot or cold exposure, prolonged hunger, high intensity exercise, etc. Our body has adaptive genes that activate boosters to cope with these minor stress events and minimize damage to the system. At a sweet spot of the amount of stress Hormesis leads to house cleaning with activation of autophagy and mitophagy. This recycles senescent cells and leads to mitogenesis. It also activates Nrf2 which releases enzymes that reduce the burden of reactive oxygen species ROS amongst 200 other beneficial gene expressions. It protects against age related chronic disorders including diabetes, middle aged obesity, cardiovascular disease, cancer and neurodegenerative diseases (Mattson, 2008). This post is not a detailed study of hormesis but a layman's update about benefits of hormesis and how one can take advantage today. So there are many other beneficial hormetic actions but the above examples illustrate their purpose. It launches a cascade of renewal including stem cell renewal, release of beneficial enzymes and hormones (for example an oxytocin bath) and clean up of wastes which allows the system to use it's full resources to recover from the stress. For a more comprehensive understanding of hormesis please read posts on the blog 'Anti Aging Firewalls' by Vincent Giuliano. You can also read 'Hormesis, Adaptive Epigenetic Reorganization, And Implications For Human Health and Longevity' by Alexander Vaiserman published in 2010 in Dose Response. Hormetic response is only available against stress up to a certain threshold with regards to intensity and time. It has a sweet spot or narrow  range where it leads to an over compensation. The beneficial cascade not only helps recover from the stress but also then goes ahead and delivers system wide improvements. This over compensation is what provides all the anti aging benefits of hormesis.  Hormesis can also be seen in plants. For example when we boil raw peanuts or tomatoes their nutritive value increases in multiples. Although limited the benefits can be potent. All system wide anti aging successes seen so far in humans use hormesis. For example Calorie Restriction at identified levels creates a stress which triggers a hormetic response leading to all its studied benefits. Valter Longo director of University of Southern California Longevity Institute has published an amazing study which concludes that prolonged fasting of 7 days triggers a stem cell based repair and regeneration of our hematopoietic system. Similarly rapamycin is a poison which targets mTOR. Its inhibition due to a low intermittent dose leads to partial reversal of the damage caused by aging. mTOR is inversely related to many pathways involved in renewal and repair like Nrf2, AMPK, etc. From a different path Metformin also generates hormetic benefits. Diabetic patients on Metformin it has been found in large studies tend to outlive patients on other medicines and also non diabetics. Even the most popular health intervention exercise provides it's most powerful benefits due to hormesis. 
So can hormesis stop aging and increase lifespan. No. As we age our repair and renewal machinery begins to lose its efficiency gradually in a progressive manner. Hormesis provides boost to the repair and renewal systems. Regular use of it would slow down the loss of efficiency thereby reducing unrepaired damage and build up of senescent cells, cancer causing mutations and protein aggregates. This has shown to improve healthspan and help prevent diseases like middle age obesity, metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer, neurodegenerative disease, etc. This in turn may lead to reaching longer lifespan.  
I have started on rapamycin (Sirolimus) thanks to Dr. Alan Green (please web search for his name and rapamycin and it will lead to his website). On his website he has given his experience with rapamycin along with some very useful information about dosage, half life, strategy to avoid side effects, etc. He suggests 2 options conservative could be 3mg per 10 days. Aggressive would be 6mg per week. FDA states a elimination half life of 62 hours +/- 16 hours. So in a week it would be 2.7 half lives. If we take a shorter interval than it may lead to accumulation of the toxin which is not a good idea. Dr. Green as he says on his website ran a marathon in 4 hours at age 40 but by the time he reached 70 his physical activity was restricted to walking his dog. At age 72 he experienced angina and shortness of breath - his fasting blood sugar was high, creatinine was high and he could not fit in any of his pants. He discovered rapamycin and Koschei through Blagosklonny. He decided to take the aggressive approach. He shared that the results in 4 months were miraculous: he lost  20 pounds, his waist line went from 38 to 33 inches. He could walk 5 miles a day and ride bike over hills without angina. His blood sugar and creatinine went back to normal. He reported no side effects (no mouth sores). He felt from feeling old to feeling young. He has called rapamycin the world's greatest medicine. I have had a few exchange of messages with Dr. Green on an anti aging forum and can vouch that he is skeptical of all science unless it has shown replicable evidence. Someone younger may want to consider the conservative approach. Of course rapamycin and metformin both are prescription drugs and must be taken only after consulting your doctor. I personally started with 1mg and after 9 days taken 2mg and have now stabilized at 3mg. Also space weights training and other heavy exercise away from rapamycin days. It is important to do exercise as that too produces hormesis and allows us to make the most of taking rapamycin. Let me give you an example. In our middle age rogue macrophages block signal from our brain to our visceral fat cells to burn fat when we need energy for example during exercise. But when rapamycin benefits reconnect the signal it will not do any good unless we create an energy demand by doing intense exercise. With regards to Metformin one can create a hormetic effect every day whereas in the case of rapamycin there would be a tapering off between doses as part of the cycle. Not yet come across a study comparing the hormetic benefits between the two. Life Extension foundation has a good web page discussing metformin dosage for non diabetics at: 
They mention 500 mg twice a day for anti aging benefits for non diabetics but some scientists believe such benefits start only at 1,500 mg a day divided in 3 doses. To be noted that anyone having liver, kidney or congestive heart failure should not take this. One must also consider that no human trials have been done in either specifically for their anti aging benefits. That doesn't mean hormetic benefits are speculative but it leaves a gap with regards to ideal dosage for optimum benefits and safety. My personal opinion is not to take both rapamycin and metformin as too much of mTOR inhibition too is not good. When one does weights training one needs the growth with an activated mTOR. An article by Blagosklonny published in Aging 2010 cites two studies that show that inhibition of mTOR beyond a certain level causes depletion of male hormones which would adversely affect ones sex life. Therefore it may be better to have a cyclic intervention like rapamycin with a 10 day interval rather daily dose of metformin. One can investigate whether cyclic dosing of metformin provides similar benefits. I do take DHEA about 4 days away from rapamycin to make up for any deficiency in testosterone.  People as young as 35 are starting on one of the two to protect their future from age related diseases but one must avoid such mTOR inhibition in younger than 35. Many scientists wrongly believe that chronic inhibition of mTOR during aging leads to sustained anti aging benefits. Even when we are young mTOR swings between activation and inhibition based on its role as an important sensor. Insulin, cytokines, nutrients, and tesosterone stimulate cellular growth in part by activating the mTOR pathway. At puberty there seems to be optimum balance between mTOR activation for growth and mTOR inhibition for repair. As we age due to falling levels of repair the balance is lost which leads to over activation of mTOR. All we need is either intermittent activation of repair (a strategy my venture is pursuing) or intermittent inhibition of mTOR. Either action should lead to reduction of their imbalance. Which in turn should slow down the epigenetic drift - and in turn aging itself.
With regards to hormesis what is exciting though is that for the aging this system wide benefit is available today! One could begin to benefit immediately.
This is not a cure for aging or death but is still the most significant recourse available today for humans to improve old age. If we can slow down aging we may be alive when the cure for aging is discovered. In the future people will see old movies just to find out about the disease of old age and gasp at how horrible it made us look and feel. My venture to hunt for the cure just progressed further - We have a CTO who is a Professor of Natural Sciences from 23 years of a highly reputed USA University and we just signed a research collaboration agreement with a very highly reputed University for pre-clinical trials - 14 in all. We are awaiting Ethical Committee approval and hope to launch by first week of December. Wish us luck. We are developing nature or endogenous derived interventions that also inhibit mTOR like rapamycin and metformin but indirectly by upregulating or activating key repair pathways. It seems that Repair and activated mTOR are inversely related. Our interventions are expected to have amongst the highest upregulation of beneficial gene expressions available. On a separate note I was asked what will you look for if you were able to live longer. I said: Purity. The most prized human trait after unsolicited acts of kindness.

Saturday, 7 October 2017


Reversing Epigenetic Silencing of Tumor Suppressor Genes

FDA approved Cardiac Glycosides for heart related ailments have turned out to be novel and exciting therapy for cancers which can be prescribed to you today by a knowledgeable and confident oncologist. 

I have recently become a fan of Dr. Jean-Pierre Issa of Temple University, USA. His recent paper on 'Caloric Restriction delays age related methylation drift' in Nature published on 14th September 2017 explains how the rate of changes in our epigenome as we age impacts our lifespan. Caloric Restriction slows that drift and so does rapamycin explaining their life extension benefits in humans.

In his earlier study published in Cancer Research in March 2016 called 'Targeting Calcium Signalling To Induce Epigenetic Reactivation Of Tumor Suppressor Genes in Cancer' Dr. Issa and his colleagues uncover the mechanism by which Cardiac Glycosides reverse epigenetic Silencing of Tumor Suppressor Genes. Dr. Issa screened 1,100 FDA approved drugs to find the ones that reversed the Tumor Suppressor Gene Silencing. They found 11 out of which Proscillaridin A a Cardiac Glycoside was the most potent. Surprisingly the action is effected through the calcium signalling pathway. When calcium levels rise above a certain threshold they activate a very interesting protein called Calmodulin. Calcium-Calmodulin Kinase activity leads to nuclear exclusion of MeCP2. Basically unlocking the promoter of Tumor Suppressor Genes and thereby increasing it's expression. As we age for unknown reasons certain beneficial gene expressions are silenced by methylation of their promoter region. Cells mutate every day and can turn into cancerous cells but Tumor Suppressor Genes eliminate them before cancers are formed.

Interestingly Calmodulin also activates DNA repair and so does tumor suppressor genes. DNA mutation caused by unrepaired lesions is one of root causes of many age related dysfunctions and diseases. This just goes to show how cancer and aging are closely related in many ways. Finding such agents which can reverse detrimental epigenetic changes as we age can lead to the next wave of anti aging therapies that actually work in humans.

There are many studies that confirm the ability of Cardiac Glycosides to send cancers into remission. One example: published in Oncotarget 2014 'Proscillaridin A is cytotoxic for glioblastoma cell lines and controls tumor xenograft growth in vivo' by Figarella Branger and colleagues demonstrates that even at low intravenous doses Proscillaridin A a FDA approved Cardiac Glycoside resulted in cancer cell death, self-renewal blockade in all glioblastoma cell lines. Glioblastoma is difficult to treat and usually has relapses so these results are significant. Such results have been seen in breast and colon cancers as well in separate studies.

Proscillaridin A is plant derived. There are other natural herbs and spices which also have shown reverse silencing of Tumor Suppressor Genes. A Review Article by
Kitagashi, Kobayashi and Matsuda published in the Journal of Oncology in 2012 titled 'Protection Against Cancer With Medicinal Herbs via Activation of Tumor Suppressor' lists many herbs and spices like Honokiol, Curcumin, Klangaite, Thymoquinone,  Triptolide, Bsicalin and Trycosanthin which reactivate Tumor Suppressor Genes. As a reader pointed out these can be taken as preventive remedies as we age.

What is very exciting for cancer patients and the reason for my post is that Cardiac Glycosides like Proscillaridin A are approved by FDA (for heart related ailments) which means they have passed safety and efficacy standards. This means cancer patients can get this benefit today under medical supervision of their oncologist! 

Sunday, 25 June 2017


CANCER & AGING: II. Aging Starts at 15 and not 50!

AGING: Two clues have emerged that shocked me with the realisation that aging starts just after puberty! These two studies also add two more evidences that aging is not due to accumulation of errors or wear and tear over time but due to direct missiles fired by pre-installed instructions just after the formation of reproductive organs. One of them collapses the support system to the protein formation machinery and the other attacks the heart cells. These are just two that have been discovered but there must many more such secret attacks that begin the process of deterioration of our biology.
After water proteins have the second highest weight in our body. There are probably more than 30,000 types of proteins that are manufactured from our DNA and the proteasome machinery that do multiple tasks including transcribing and translating instructions from our genes to our cells, act as hormones, enzymes and part of immune system. Proteins are born in long strips which are then folded into a particular shape. This shape decides it’s function. If there is misfolding it can become damaging. So nature has added multiple chaperones to help it fold correctly and if any still slip by then to avoid damage they are degraded by ubiquitin protease system and autophagy. Soon after puberty Germline Stem Cells GSCs send a signal to this important support machinery to collapse it’s efficiency by as much as 70%. This seems to be the first identified assault of aging. From then onwards more and more proteins come out misfolded and worst are not degraded so clump together to create sticky aggregates which disturb many cellular functions leading to damage and disease.

The ribosome makes mistakes in as many as 1 in every 7 proteins! Even under normal conditions, up to 30% of all cell proteins fail to fold properly, and are immediately degraded. Protein folding is a very sensitive process that is influenced by several external factors including electric and magnetic fields, temperature, pH, chemicals, space limitation and molecular crowding. These factors influence the ability of proteins to fold into their correct functional forms.
Scientists have pinpointed the start of aging and discovered it is not a slow series of random events. Two Northwestern University scientists have identified a molecular switch in the transparent roundworm C. elegans, that abruptly begins cell aging just as the animal reaches reproductive maturity.
A genetic switch starts the aging process by turning off the cell's ability to respond to stress. Responding to stress would otherwise protect a cell by keeping essential proteins folded as well as functioning. The switch is thrown by germline [sperm and egg] stem cells in early adulthood, after reproduction begins.
While the studies were conducted in worms, the genetic switch and other components identified by scientists as part of aging, are conserved in all animals — including humans. And as C. elegans has a biochemical environment similar to our own, it is a popular animal model for human disease and for human aging.
"Wouldn't it be better for society if people could be healthy and productive for a longer period of their lifetime? I am very interested in keeping the quality control systems optimal as long as we can, and now we have a target. Our findings suggest there should be a way to turn this genetic switch back on and protect our aging cells by increasing their ability to resist stress." said Richard Morimoto PhD, the Bill and Gayle Cook Professor of Molecular Biosciences, director of the Rice Institute for Biomedical Research, Weinberg College of Arts and Sciences, Northwestern University.
Once the germline has completed its job and 1) produced eggs and sperm needed to create the next generation, it 2) sends a signal to cell tissues to turn off protective mechanisms and begin the decline of the adult.
In one experiment, researchers blocked the germline from sending the signal to turn off cellular quality control, and found the somatic tissues remained robust and stress resistant.
Morimoto: "This was fascinating to see. We had, in a sense, a super stress-resistant animal that is robust against all kinds of cell stress and protein damage. This genetic switch gives us a target for future research."
Study’s finding that the loss of stress protection responsiveness in C. elegans is a result of failure to clear a single repressive chromatin modification, which interferes with a heat shock factor (HSF-1) binding event, which in turn suppresses transcription initiation in response to stress.
The molecular mechanism is particularly intriguing, as it involves a signal from germline stem cells that decreases expression of a specific demethylase enzyme, resulting in elevated levels of a repressive class of histones targeted to the genes for cell stress responses.  The consequence: a rapid, coordinated inhibition of stress survival mechanisms.”
Here again we see what I pointed out in my last post Mechanism of Aging - Nature's calibration happens through tuning of activators and inhibitors.
They demonstrate that HSF1-promoter accessibility sharply declines on the second day of adulthood. This is strongly associated with sharply increased levels of H3K27me3 marks at the promoters of heat shock genes, a hallmark of transcriptional repression [that results in dysfunctional protein production]. This demonstrates, for the first time, that the repression of the heat shock response is regulated, and that epigenetic changes modulate the animals’ ability to respond to stress after reproduction onset.” “discovered that enhancing this demethylase (jmjd3.1), which is conserved to humans, prevents this decline in stress resilience, and results in animals both robust and long-lived.”
In a separate study Lead author Dr Sean Byars from the University of Melbourne says the team wanted to understand more about how CAD (coronary artery disease) has been inherited in our evolutionary past, in order to better understand why it is so common presently. "CAD is often thought of as modern disease, but actually atherosclerosis, or thickening of the artery walls, has been detected in Egyptian mummies, so we suspect it has been in our genes for thousands of years."
CAD currently affects 110 million people and causes 8.9 million deaths annually, from 2015 figures.
"According to the theory of natural selection, as proposed by Charles Darwin, genes for traits that improve individual survival or reproduction will increase or be maintained in populations, whereas those that reduce these will be selected against and gradually removed or reduced over time. "So it is unclear why CAD is so common in modern humans and this is important to understand given the global health burden it represents," explains Dr Byars.
Associate Professor Michael Inouye, who also led the study, said the findings showed that many genes associated with CAD have actually been positively selected for through evolution.
"After further research, we found CAD genes are also important for reproduction and that these genes are involved in important functions in male and female fertility being expressed in the testes, ovaries and endometrium, for example," said Assoc Prof Inouye, based at the Baker Heart and Diabetes Institute.
So in this case too same genes which were important and beneficial during reproduction biology later flip a switch and become very harmful by causing CAD – the leading killer in humans.
These studies show that for Nature once the primary function of reproduction is done the body becomes only a competition for resources for the new born and is to be bumped off. What is shocking is that aging begins its damage just after we reach reproductive maturity – puberty. By the time we begin to see the effects of this build up of damage around 50 years of age it is already too late and a lot of the damage is done. Although this shows how complex is aging disheartening the anti aging crusaders, a clue also emerges: the changes that initiate the damage are actuated by new epigenetic marks. A permanent cure for aging may lurk in the corridor of the epigenome and the transcription factors.


CANCER & AGING: I. Combination Therapy – a complete cure for Cancer?

When I started deep research I used to regret not being a PhD because almost all scientists seem to be PhDs. But now I feel that it has been a blessing as it has allowed me to be able to view a research topic in 3D. Almost all PhDs specialise and narrow focus to create expertise in a particular niche. Nothing wrong with that and great discoveries have resulted from such an approach. But for working towards curing a disease ability to learn and analyze on a multifactorial basis it seems improves the chances of finding a cure rather than incremental benefit.
My thirst for knowledge and research continues to rise by every passing day it seems. In my leisure time if I have an option to either watch a movie, read a book or discover new music I end up choosing to research. Either thats where I get my highest pleasure or I have probably become a scientist in heat. Probably entering the last mile of a scheduled jump in clinical validation of my scientific discoveries.
In my research journey I continue to evolve my knowledge about a target and my own conclusions about it. So there are studies and there are studies but some become milestones after which we view the subject with new eyes like Sinclair’s NAD+, Conboy's parabiosis, Katcher's HPE and Hayashi's reversal of aging cells with glycine. Today I want to share two posts which cover studies which should have been ranked as major breakthroughs but may have been missed in the clutter.
My spotlight is on the two subjects I have done the most posts on this blog: cancer and aging. The irony is that both are highly related and are in fact two sides of the same coin. Unchecked growth can lead to cancer and systemic decay is a hallmark of aging. Let’s first look at cancer:
CANCER: Cure for cancer may emerge from a combination therapy of immunotherapy and blocking proteins that help cancer metastasis. Metastasis is behind 90% of cancer deaths. I have covered immunotherapy in my earlier post. Today I want to share a remarkable study:
Hasini Jayatilika a post doctoral researcher at John Hopkins came out with a brilliant conclusion: Metastasis occurs not after the tumour reaches a certain size as it is believed but due to tumour density. During a lecture while she was still studying at John Hopkins she saw a similar diagram regarding how bacteria proliferate. She tried to find some study in cancer showing that. Couldn’t find it so she took up that hunt herself. 7 years of research and she  demonstrated how after reaching a certain density tumour cells begin to release two proteins Interleukin 6 and Interleukin 8. They tell the new cancer cells that it is getting too crowded separate out and build your own nest at some other site. She observed this after studying the communications between cancer cells.

She and her Professor Denis Wirtz found out that all the cancer therapeutics were being built to target the primary tumour and no one was working drugs that could block the metastasis. They then themselves set out to test two already approved drugs which were known to work on the Interleukin receptors called Tocilizumab a rheumatoid arthritis treatment and Reparixin a potential cancer drug. When combined they seemed to significantly slow down the metastasis. Hasini feels that some tuning or another combination could potentially stop all proliferation completely. The amazing thing is that this may be applicable to all solid tumours. This is very good news for cancer patients as 90% of cancer deaths are caused by metastasis. My blog post “Goodbye Chemotherapy” already discussed how immunotherapy can attack only the cancer cells. But as I had pointed out in a following post about metastasis and mother cells – the cancer stem cells causing the lethal proliferation which may not be addressed by immunotherapy alone. With this combination therapy of immunotherapy and blocking of interleukin 6 and 8 proteins there might be complete cure which may prevent a relapse after clearance. All patients with solid tumours should talk to their doctors about the feasibility of prescribing this combination to put a break to any event of metastasis. Of course keep in mind that although both are approved drugs a combination therapy for metastasis has still not been approved by FDA. Another good news is that these drugs do not cause the horrible side effects of  chemotherapies. So a doctor may make their own decision based on patients parameters and each drugs safety profile. I rate this as a major breakthrough for cancer survival making Hasini a rock star hero for cancer patients worldwide.

Tuesday, 18 April 2017


                    MECHANISM OF AGING

                  Can we grow young again?                            Trials that can change the lives of billions

I have formed a view regarding the mechanism of aging, not the switches that turn it on, only the mechanism. In our body DNA damage is very frequent, occurring on average about 60,000 times a day per cell of the human body but this is not the cause of aging. The rate of damage is the same for the young and the old - what changes as we age is the rate and efficiency of repair. At any given moment, there's competition in your body between cellular damage and repair. As the damage becomes greater than your body's ability to repair and regenerate, deterioration sets in. "If we could repair damage as fast as it occurs, we could live forever," says Dr. Rosedale. Another competition is between growth and repair. When one is dominant the other is muted. Too much repair beyond what is needed can become harmful to healthy cells and so is too little. So Nature has created activators and inhibitors and sensors. In our prime the opposing forces move the steering wheel left and right efficiently so that the repair car remains in the middle of its lane but as we age one begins to dominate the other (for example inhibitors overpower the activators) causing the snowballing feedback loops and dysfunctions which slacken the pace of repair, on a sliding basis, leaving unrepaired damage. Their dysfunction increases systemic damage including to the organs. What would happen if the steering wheel is pulled only on one side more and more? The repair car will soon veer off road and sooner or later is destined for a fatal accident. Yin and Yang a 3rd century BC gift of Taoism figured out Nature's system of opposing forces maintaining an equilibrium - agonists and antagonists, push and pull - how seemingly opposite or contrary forces may actually be complementary, interconnected and interdependent in the natural world and how they may give rise to each other as they interrelate to one another - as described in Wiki. Multiple reactions with intricate networks of activators and inhibitors are involved in biological homeostasis. Homeostasis is maintained by a series of control mechanisms functioning at the organ, tissue or cellular level. These control mechanisms include substrate supply, activation or inhibition of individual enzymes and receptors, synthesis and degradation of enzymes and compartmentalization. Despite its complexity biological systems are after all finite. And all finite problems can be solved. Restoring the equilibrium found in our prime between damage and repair can cure aging. When young blood is transfused in old it temporarily rejuvenates the equilibrium of the repair systems by the circulating young factors. But the transcriptional program resumes destabilizing the balance between the opposite forces to ensure repair gets weaker again and progressively. Clearing senescent cells or lengthening telomeres or upregulation of NAD+ are resurrecting some parts of the dysfunction. Only restoration of full equilibrium in the repair machinery vis-a-vis damage can cure aging as a whole. 
An example: A recent exciting development in the field of anti aging has been the discovery of a molecule called FOXO4-DRI by
Cell biologist Peter de Keizer of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues. When the cells face damage, repair machinery remedies the damage and revives the cell. Sometimes the damage is beyond repair. At such time cell adopts a process called Apoptosis and dies or is recycled by a process called Autophagy. If for any reason a severely damaged cell misses both, the cell becomes a zombie - senescent cell. Senescent cells secrete poisons which affect surrounding healthy cells. As we age and the forces inhibiting our repair systems begin to dominate over repair activators it begins to reduce our repair efficiency.  This creates more and more senescent cells. They tend to clog our tissues and organs and cause progressive damage to them. But Nature has made a cure for them to keep a check on how many senescent cells remain. P53 is a tumour suppressor protein that binds to senescent cells and helps them achieve apoptosis. But as we read above Nature keeps a inhibitor to ensure there is not too much of P53. This is another protein called FOXO4. It binds to P53 and blocks it's ability to help senescent cells achieve apoptosis. In our prime the opposing forces of P53 and FOXO4 balance at levels to create optimum clearance of senescent cells. As some amount senescent cells are needed for wound healing and they are also a valuable raw material in the genesis of new cells. But as we age this balance too is disturbed wherein too many of the P53 inhibitor FOXO4 are produced which in turn multiplies the numbers of senescent cells which continue to multiply the damage in the system, tissues and organs. This is a classic example of the Yin and Yang losing its optimal balance. FOXO4-DRI is a synthetic molecule that has higher affinity for P53 - it wins the competition with FOXO4 in binding with P53. This allows P53 to complete it's task of enabling senescent cells achieve apoptosis. It has shown remarkable reversal in certain aging markers on mice. Old mice regained thick coat of fur seen in young mice and were able to do tasks that they did when they were young. An intervention that restores the optimum balance between inhibitors and activators can potentially undo damage and reverse aging helping us regain our youth.
Another Example: PARP1 is an enzyme that is essential in initiating various forms of DNA repair. DBC1 binds to PARP1 and prevents it from executing DNA repair. So it becomes a inhibitor. Each inhibitor should have a corresponding activator - in this case NAD+ plays that role. NAD+ prevents DBC1 from binding with PARP1 and thus ensures DNA repair. As we age the levels of NAD+ decreases by which increases the binding of DBC1 with PARP1 the result: DNA breaks go unrepaired and as these breaks accumulate over time, precipitate cell damage, cell mutations, cell death, and loss of organ function. David Sinclair’s lab at Harvard Medical School observed that when NAD+ levels were restored the markers showed improved DNA repair. Thus here too we see that restoring the optimum balance of inhibitors and activators brings back youthful levels of repair. 
As we age we see our body shape, fitness, skin, hair and our face change gradually but visibly. When we compare our photos of age 25 and age 75 we look so dramatically different - we find our 25 year old self better looking and more attractive. The difference between the two is the damage that slips by the repair machinery. One can see how mercilessly it chisels away the radiant beauty of youth. Since we have seen others also suffer this damage without question we too accept this trauma and tragedy as normal. A few tweaks may be all that may be required to not only avoid these debilitating changes but potentially reverse them. We assume that all of us is as old as our age but except for neurons of the cerebral cortex we are not more than 15 years old. As everything inside us renews and recycles itself. Sperms life is only 3 days, taste buds 10 days, lungs 3 weeks, skin which carries our outward appearance just 2-4 weeks, liver 150 days, bones 10 years, etc. We always look at reversal of age very sceptically but now that you have this perspective it brings it back in the realms of possibilities. So my question is: if damage caused by aging is reversible (as confirmed by recent studies Hayashi Tsukuba University) and if we are able to bring back the optimum balance between repair system inhibitors and activators why would a 75 year old not begin to look and feel like his 25 year old self again??? My venture is hoping for that to happen. In collaboration with a reputed University we are launching pre-clinical trials on old lab mice where my proprietary protocol of interventions (a fruit of many years of research and analysis) may bring back the optimum performance of their repair systems. Hopefully this in turn may make the old mice young again. There have been many anti-aging experiments around the world which have been able to extend the life of lab mice by 5% to 50%. Our quest is to maintain repair system biochemical homeostasis and keep the reversal to youth sustainable. I will be able to update you with the results within a few months. The tests are for safety, dosage, bioavailability and efficacy. If we are successful we plan to conduct human clinical trials next in collaboration with a reputed hospital. Wish us luck and success

Sunday, 28 February 2016


2nd of the two biggest debates of biomedical world: Are we programmed to die?

DEBATE II: Do we die because we succumb to wear and tear of our biology over the years or due to a DNA code programmed in us before we were born? Longevity has a good explanation for this theory: The wear and tear theory of aging believes that the effects of aging are caused by damage done to cells and body systems over time. Essentially, these systems "wear out" due to use. Once they wear out, they can no longer function correctly. It was first expressed in science by German biologist Dr. August Weismann in 1882. We simply expect that the body, as a mechanical system, is going to break down with use over the years. 
A range of things can damage body systems. Exposure to radiation, toxins, and ultraviolet light can damage our genes. The effects of our body's own functioning can also cause damage. When the body metabolizes oxygen, free radicals are produced that can cause damage to cells and tissues. There are some cellular systems that don't replace themselves throughout life, such as the nerve cells of the brain. As these cells are lost, function eventually will be lost. Within cells that continue to divide, the DNA can sustain damage errors can accumulate. Simply the act of dividing again and again shortens the telomeres of the chromosomes, eventually resulting in a senescent cell that can no longer divide. Oxidative damage in cells results in cross-linking of proteins, which prevents them from doing the jobs they are intended to do in the cells. Free radicals inside mitochondria, the powerhouses of our cells, injures their cell membranes so they can't function as well. 
Not all damage can be repaired fully, and mistakes in repairs may accumulate over time leading to our death.

Programmed aging and death theory is based on aging related slow decline of cellular functions being caused by a epigenetic clock programmed into our DNA. One major development in a Japanese lab of Jun-ichi Hayashi from Tsukuba University may tilt the scales towards this theory. The Tsukuba team has performed some compelling research that has led them to propose that age-associated mitochondrial defects are not controlled by the accumulation of mutations in the mitochondrial DNA but by another form of genetic regulation. The research, published this month in the prestigious journal Nature’s ‘Scientific Reports’, looked at the function of the mitochondria in human fibroblast cell lines derived from young people (ranging in age from a fetus to a 12 year old) and elderly people (ranging in age from 80-97 years old). The researchers compared the mitochondrial respiration and the amount of DNA damage in the mitochondria of the two groups, expecting respiration to be reduced and DNA damage to be increased in the cells from the elderly group. While the elderly group had reduced respiration, in accordance with the current theory, there was, however, no difference in the amount of DNA damage between the elderly and young groups of cells.

This led the researchers to propose that another form of genetic regulation, epigenetic regulation, may be responsible for the age-associated effects seen in the mitochondria. Epigenetic regulation refers to changes, such as the addition of chemical structures or proteins, which alter the physical structure of the DNA, resulting in genes turning on or off. Unlike mutations, these changes do not affect the DNA sequence itself. If this theory is correct, then genetically reprogramming the cells to an embryonic stem cell–like state would remove any epigenetic changes associated with the mitochondrial DNA. In order to test this theory, the researchers reprogrammed human fibroblast cell lines derived from young and elderly people to an embryonic stem cell-like state. These cells were then turned back into fibroblasts and their mitochondrial respiratory function examined. Incredibly, the age-associated defects had been reversed – all of the fibroblasts had respiration rates comparable to those of the fetal fibroblast cell line, irrespective of whether they were derived from young or elderly people. This indicates that the aging process in the mitochondrion is controlled by epigenetic regulation, not by mutations. The researchers then looked for genes that might be controlled epigenetically resulting in these age-associated mitochondrial defects. Two genes that regulate glycine production in mitochondria, CGAT and SHMT2, were found. The researchers showed that by changing the regulation of these genes, they could induce defects or restore mitochondrial function in the fibroblast cell lines. In a compelling finding, the addition of glycine for 10 days to the culture medium of the 97 year old fibroblast cell line restored its respiratory function. This suggests that glycine treatment can reverse the age-associated respiration defects in the elderly human fibroblasts. These findings reveal that, contrary to the mitochondrial theory of aging, epigenetic regulation controls age-associated respiration defects in human fibroblast cell lines. Can epigenetic regulation also control aging in humans? That theory remains to be tested, and if proven, could result in glycine supplements giving our older population a new lease of life.
Similarly David Sinclair's lab at Harvard showed that by upregulating NAD+ in the mitochondria the musculosketal infrastructure of the body rejuvennated to youthful peak levels.
Harvard's David Sinclair's Formula to Reverse Aging 
Parallely the Conboys and Wager demonstrated the rejuventation of muscles, brain, liver and other organs and systems by parabosis in two linked mice circulating young blood in old mice. Which proved that when signal proteins from young plasma circulated in an already age ravaged body were still able to reverse aging on the old mice.

The above two have been covered in my earlier post called 'Can we cure aging?' in more detail.
All the three put together provides clear evidence that aging does not create permanent damage or is not caused by wear and tear.

My Conclusion: There is a code that has been planted in the DNA of ALL living things on this planet which is triggered by a epigenetic clock and leads to decline and death of the host. Steve Horvath of UCLA has not recieved the fame and appreciation he deserves for discovering the DNA methylation clock that accurately measures human age. Various strips of DNA has codes that make us grow to adulthood from babies and later, on reproductive maturity, trigger a slow decline leading to death. I don't expect these strips to be in one long chain but in different locations. What is remarkable is zero error rate - we do not see anyone due to DNA mutations cheating death. There are errors which cause various handicaps and deformities but never ever since record of humanity have we observed an error in code regulating aging and death. This shows that Nature gives a lot of importance to death and must have programmed multiple pathways to ensure decline and death in all living things. When we upregulate NAD+ or glycine or AMPK or whatever else has been shown to prolong life in lab animals we are only trying to cure the symptoms. Which can not lead to cure of aging and avoidance of death. There are only two ways it seems that one can aim to achieve this:

1. By disrupting the epigenetic clock by infusion of plasma of a young donor into the patient wanting to reverse aging. The noch protein signals of a donor whose epigenetic clock is signaling body to works at its peak is expected to do the same for the new recipients body as seen in parabiosis models in lab mice pairs. The question is will it do the same in human parabiosis or plasma exchange? Also if it does would the new signals flooding the body in sufficient numbers be able to reset the epigenetic clock of the old human to the age of its young donor or will the benefitial rejuvenation last only up to the life of the signal proteins? If it is the former the parabiosis or plasma exhange would be needed only once every 10 years to reset the epigenetic clock back to the age of 25 (from 35) and if it is the latter then the parabiosis or plasma exchange would need to be done every 4 months.

2. The other way would be identifying which section or sections of the human DNA has the triggers for decline messages to be relayed linked to the progress of the epigenetic clock. DNA does not need to have a message for effecting death. The total body decline ensures that it leads to death. This would be quite a challenge compared to the first option which can be implemented today by any qualified physician using the plasmapheresis machine. Identifying from the 20,000 to 25,000 protein coding genes - it may be a single one that triggers a cascade or it may be multiple ones that work independently or in synergy - too many permutations and combinations to evaluate. It may also be from the huge amount of non coding genes which now are no longer considered junk but also seem to be having some biological function. Needle in a haystack type of situation. But we have already mapped the entire human genome and have invented incredibly powerful gene editing tools like CRISPR - The importance of CRISPR - We are Nature's Robots with a software that dictates everything that happens to us - CRISPR is a tool that allows us to edit this software. We still don't know what to edit but when we do CRISPR will help us execute it.
Once the genes are identified we would need specific binding agents to block it from triggering the functional decline messages. Assuming that the identified genes also do not have other needed functions. Testing which genes play a role in triggering aging decline is very difficult to do as we can not try editing out genes on a living human. So is it impossible to eventually identify the genes triggering aging decline? Of course not. We will achieve this - it is only a matter of time.

Half a Million DVDs of Data Stored in Gram of DNAhuman longevity


One of two biggest debates of the biomedical world (second debate covered in separate blog post)

DEBATE I: Are all cancer cells mutagenic and proliferative or only the core mother stem cells? 
Dr John Dick sparked this debate in 1994 when he isolated the first cancer stem cell, and showed that these rare cells cause leukemia to grow in mice. Researchers at the University of Michigan made the case in 2003 that the same was true in breast cancer. In 2004  Dr Dirk a scientist and neurosurgeon at Toronto's Hospital for Sick Children discovered cancer-causing stem cells in the brain tumours of mice. The idea began gaining wider acceptance that a tiny number of cancer stem cells cause cancers to grow. As reported in Wkipedia under Cancer Stem Cells (CSCs): CSCs may generate tumors through the stem cell processes of self-renewal and differentiation into multiple cell types. Such cells are hypothesized to persist in tumors as a distinct population and cause relapse and metastasis by giving rise to new tumors. The theory suggests that conventional chemotherapies kill differentiated or differentiating cells, which form the bulk of the tumor but do not generate new cells. A population of CSCs, which gave rise to it, could remain untouched and cause relapse. The debate over the existence of a minority of CSCs at the root of all cancers or not has been continuing since the last 12 years. Both sides have been citing lab and murine studies to validate their argument. One example for each:

Evidence for Refuting the CSC theory: Sean Morrison director of the University of Michigan Center for Stem Cell Biology and his team of researchers  have determined in Nov 2010 that most types of melanoma cells can form malignant tumors, providing new evidence that the deadliest form of skin cancer does not conform to the increasingly popular cancer stem cell model. In addition, the researchers found that melanoma tumor cells can change their appearance by switching various genes on and off, making the malignant cells a stealthy, shape-shifting target for researchers seeking new treatments. As reported in Michigan News Both findings fly in the face of the cancer stem cell model, which states that a handful of rare stem cells drive the formation, growth and progression of malignant tumors in many cancers. Some supporters of the model have suggested that melanoma might be more effectively treated by taking aim specifically at these rare cancer stems cells, rather than attempting to eliminate all melanoma cells. But after conducting an exhaustive search for this elusive sub-population of tumor-forming melanoma cell, the U-M team concluded that it probably does not exist. The researchers analyzed 44 sub-populations of human melanoma cells, and all 44 had a similar ability to form tumors when transplanted into mice. "Some have suggested that melanoma follows a cancer stem cell model in which only rare cells are able to proliferate extensively and form new tumors. Our results suggest that most melanoma cells are capable of driving disease progression and that it won't be possible to cure patients by targeting rare sub-populations of cells," Morrison said. "We think you need to kill all the cells."
Are all Melanoma cells are cancer stem cells in disguise? Melanoma cells under an elctron microscope
The study found that tumor-forming melanoma cells have the ability to throw a genetic switch that changes the types of proteins expressed on the cells' surface. The study is the first to present evidence for this type of pervasive "phenotypic plasticity" among melanoma cells from patients. Patterns of surface proteins are used to identify different cell types and are commonly called cell surface markers. "The fact that these markers are turned on and off by melanoma cells raises the possibility that melanoma cells may also turn on and off genes that regulate clinically important characteristics like drug resistance and metastatic ability," Morrison said. "The ability to transition between various states may make melanoma more difficult to treat." The authors stress that while their results argue against a cancer stem cell model for melanoma, their findings do not invalidate the model. In fact, certain leukemias and other cancers appear to follow the model.
"It will be critical to determine which cancers follow a stem cell model and which do not, so therapies designed to target rare sub-populations of cells are not inappropriately tested in patients whose disease is driven by many diverse cancer cells," Quintana also from the UM Stem Cell Center said. "The cancer stem cell model says that tumor cells are organized hierarchically, and that only the cells at the top of the hierarchy form tumors. Cells at the bottom of the hierarchy can't," Morrison said. "In our model, all these cells can form tumors," he said. "And they're phenotypically different from each other not because they're hierarchically organized but because they're just turning these surface markers on and off." The U-M team found that all tumor-forming melanoma cells gave rise to progeny with a variety of marker patterns, and that all of those sub-populations retained the ability to form tumors. The marker changes appeared to be reversible, rather than being associated with a transition from tumor-forming to non-tumor-forming states, as the cancer stem cell model would predict.

Evidence for existence of CSCs and their role in cancer: In a study published in the journal Cancer Cell in 2014, researchers at Oxford University and Sweden’s Karolinska Institutet said they had tracked gene mutations responsible for a form of blood cancer back to a distinct set of cells which they say are at the root of the cancer’s spread. 'It's like having dandelions in your lawn. You can pull out as many as you want, but if you don't get the roots they’ll come back,' explains first author Dr Petter Woll of the MRC Weatherall Institute for Molecular Medicine at the University of Oxford. The 15 patients involved in the study had myelodysplastic syndrome (MDS), a blood disorder which causes a drop in the number of healthy blood cells, and develops into acute myeloid leukaemia in around half of all cases.
Cancer cell and lymphocytes
Genetic tracking identifies cancer stem cells in patients. Photo: University of Oxford

Researchers investigated malignant cells in the bone marrow of the patients and tracked them over time. Using genetic analysis, they were able to isolate a small and distinct group of MDS cells which were the origin of the cancer-driving DNA changes which were causing the disease to progress. 'This is conclusive evidence for the existence of cancer stem cells in myelodysplastic syndromes,' says Dr Woll. 'We have identified a subset of cancer cells, shown that these rare cells are invariably the cells in which the cancer originates, and also are the only cancer-propagating cells in the patients. It is a vitally important step because it suggests that if you want to cure patients, you would need to target and remove these cells at the root of the cancer – but that would be sufficient, that would do it.'Dr Peter Woll, first author, said that it did give future researchers “a target” for development of more efficient “cancer stem cell-specific” therapies. However, even if cancer stem cells were eliminated, Dr Woll added, there would still be a chance that genetic mutations could lead to other stem cells later becoming cancer stem cells. Professor Kamil Kranc, a Cancer Research UK stem cell expert based at the University of Edinburgh, said that the findings were a “a huge leap towards understanding the roots of blood cancers”. Dr Neil Rodrigues, of the European Cancer Stem Cell Research Institute at Cardiff University, said that the new study was “very important”, as it “precisely defines the provenance and biological composition of the cancer stem cell in MDS.”

Leader of the Pack: There are more than a dozen companies that have reached clinical trials in patients specifically targetting cancer stem cells including Boston BIomedical which was acquired by Dainippon Sumitomo Pharma Co. for US$ 2.63 billion and Oncomed at US$ 300 million valuation on NASDAQ.
The leader of he pack of cancer stem cell tergetting biotech companies is Stemcentrix. It has achieved an astounding valuation of US$ 5 billion without any sales and has raised half a billion dollars. This Californian start up is backed by heave weight investors Fidelity Investments, Artis Ventures, Silicon Valley Bank, Sequoia Capital, Elon Musk,  and a US$ 200 million investment from one of the most successful investors in the world Peter Thiel and his Founders Fund (earlier co-founder of Paypal, dscovered Facebook and invested in AirBnB and Palantir).
Scott J. Dylla
Scott Dylla co-founder Stemcentrix
Image result for brian slingerland stemcentrx
Brian Slingerland co-founder Stemcentrix
Image result for peter thiel
Peter Thiel The backer with the midas touch
Stemcentrx, formed in 2008, is developing a small-cell lung cancer therapy that homes in on a target, DLL3. The product, which uses an antibody to guide a cell-killing drug to its target, appears to be effective in some small-cell lung cancer patients. In a recent trial of 80 small-cell lung cancer patients, which was testing safe dosage, tumors shrank more often than they did in response to the only approved drug to treat the cancer, topotecan. For patients whose cancer exhibits the stem-cell marker the drug aims at, benefits were larger. It’s one of three drugs the company is already testing in human trials. Why do top investors put in so much money at such crazy valuations in such early stage highly risky venture? Probably based on the success of Pharmacyclics Inc., a cancer drug developer that was acquired by AbbVie Inc., for $21 billion in May 2015. Scott Dylla an ex Stanford stem cell targetting researcher and ex tech banker Brian Slingerland co-founded Stemcentrix. All this smart money is betting that CSCs are present in cancer biology and play the role of the mother bee in a beehive.

My conclusion: Both sides are showing evidence in this debate. It is finally irrefutable results in human clinicals of stem cell targetting drugs that will put in the last word. It may be that both are right. Different cancers may have different biologies some with CSCs and some without. Or cancer may be the most scary shape shifter of them all constantly changing its avatar. But if the CSCs are the cause of all recurrences of resistant cancers and we can kill the CSCs with allopathic and natural drugs then we may be able to save millions of lives.

I leave you with some useful information from European Cancer Stem Cell Research Institute at Cardiff University:

Diagram showing how cancer stem cells could arise
This shows how a normal stem cell creates a new stem cell and a progenitor cell. The normal progenitor cell then matures into differentiated (specialised) cell required by the body. An event such as a direct genetic mutation or effect from external factors could make these cells mutate or de-differentiate i.e. lose their specialisation at any stage. These affected cells could then produce a cancer stem cell. (With inspiration from Therese Winslow’s artwork)

Cancer stem cell theory
his shows the initial theory of how cancer stem cells can maintain a tumour. Even with conventional cancer therapy the cancer stem cells survive and the cancer can relapse but if we can identify cancer stem cells and develop specific treatment the patient outcome could be improved as the tumour would regress or enter remission.

Cancer stem cell theory 2
This shows another theory of how cancer stem cells can conserve a tumour. There may in fact be more than one type of cancer stem cell so with conventional cancer therapy the tumour mass is maintained. But again if we can identify cancer stem cells treatment could be improved.

Tumour regression
Pictures from Dr Richard Clarkson (Cardiff University) showing how Cancer Stem Cells grown in the laboratory can be killed over time – a model of tumour regression.

Sunday, 21 February 2016


A Safe Weapon for Every Cancer Patient

Cancer is one of the most potent diseases that afflicts us. The scary part is the rapid mutations that cancer cells do which help them survive various chemotherapies. Even if a small invisible number of cells survive they rebound again resistant and stronger than before which makes cancer such a sophisticated and dreaded killer. Recent evidence has shown the existence of Cancer Stem Cells CSCs.
Cancer Stem Cells CSCs under a microscope
 Like other stem cells, cancer stem cells possess the ability to differentiate into various different cell types. In the case of cancer, stem cells differentiate into the various malignant cells that make up a tumor colony. Although they make up less than 1 percent of the cells in any given tumor, stem cells are immune to nearly all known or experimental chemotherapy agents. These cells are also able to replicate indefinitely, and they are capable of splitting off from their originating colony to start new tumors elsewhere.

They are key players in the process of metastasis, which is responsible for 90 percent of cancer-related deaths. New path to eliminating cancer by way of immunotherapies is giving us tremendous hope of finding a way to outsmart this killer (covered in my earlier post Goodbye Chemotherapy).
But the fear remains as we will only find out later whether the cancer stem cells can adapt to remove the receptors on the surface and inside of cancer cells which are targeted by immunotherapies. The ability of some cancer stem cells to mutate at a ferocious rate and their having a 'master switch' which helps them survive the incredible metabolic stress from such rapid mutations causes a sinking feeling to every doctor/scientist battling it.

Scheme of cancer progression
Lung Cancer stages to the dreaded Metastasis stage

DISCLAIMER: This post is for informational purpose only. I am not recommending any Natural Therapy or product. Reader must do their own research and fact finding along with consultations with their doctor before considering any therapy or product.
IMAGES: Copyright of all images belong to their original owners. They have been displayed here only for the benefit of cancer patients and their family. 
BIOAVAILABILITY: Just by taking a nutrient in some form does not guarantee it's benefits. For example adding curry to diet or taking a turmeric pill may not provide anywhere close to the dose needed against cancer and this is where most natural interventions fail. One needs to take curcumin or turmeric with piperine to ensure sufficient uptake in the body. If you decide to incorporate any natural remedy please do research on safe but effective dosage and delivery strategies or synergistic pairings to ensure sufficient bioavailability. This is when one would begin to gain the full benefits of Nature's bounty.

One of the options that is available to almost all cancer patients is to take advantage of weapons provided by Nature. What is important to note is that there are a few Natural products which have shown ability to target the elusive cancer stem cells. This can be the difference between life and death for the cancer patient. Unfortunately modern allopathic medical system does not train doctors to research and prescribe the best natural adjuvant treatment for you so cancer patients and their families have to rely on blogs like these and paid research services (cheap) like Health Cure Research which help research and identify potent Natural compounds which can target the patients cancer. Whether some of them are potent enough to become the first line of defense against cancer and eradicate it or can be used as a second line of defense to improve the survival rate of the patient the good thing about Natural therapies is that in almost all cases it has minimal side effects if any at all. It is shocking to see how intelligently the natural compounds blend in our body's bio chemistry and fulfill their tasks. Natural compounds in so many different paths selectively kill cancer cells, even the dreaded cancer stem cells but leave healthy cells without any harm. How the natural compounds have such affinities, binding precision and bio chemical structures to selectively target a mutation in our body's cells is amazing! Makes you wonder if it is a mere random coincidence or a factor of design.

As almost all nature derived products in pure form should not show side effects in their appropriate doses it makes sense for every cancer patient to research and regularly take some natural therapies along with allopathic remedies. Many highly potent natural compounds and extracts have been discovered in lab experiments in vitro and in vivo but unfortunately not many have gone further to be exhaustively tested in lab animals and humans. So a lot of the confirmation of the efficacies may come in anecdotal form. Despite this I personally believe that if safety and dosage has also been tested in the labs then it is surely worth tailoring a natural therapy program selecting the ones that have shown benefit for a particular cancer.

Synergistic combinations are an exciting and unexplored treasure waiting to be mined in the future. And by Synergy I mean both a cocktail of Natural compounds or a Natural compound paired with a chemo, surgical or radiation therapy. From the very few that have been tested some have shown remarkable success clearing 100% of the cancer within weeks if not days and deliver the same potency as a pharmacological product. Another big low hanging fruit here is prevention. Here Natural products beat Pharma completely.

Shark Tank investor Robert Herjavec said that 50% of all Americans will be diagnosed with cancer at some point in their lives! What are the odds that you should be reading this post seriously? When SARS infects 0.01% of the population we are all in panic and wear masks and call it an epidemic. What do you call when a disease reaches 50%? Cancer is the fastest growing pandemic of the modern world. Cancer prevention is the best bet and natural therapies are the only solid approach for prevention.

To get you started I have listed a selected few natural products, extracts and therapies meeting my standards of  success in experiments conducted by reputed researchers/labs or multiple peer reviewed studies published in reputed journals:

1. CURCUMIN/TURMERIC: The most potent Natural compound against cancers: curcumin appears to be universally useful for just about every type of cancer, which is really incredible since cancer consists of a wide variety of different molecular pathologies.

Curcumin modulates growth of tumor cells through regulation of multiple cell signaling pathways including cell proliferation pathway (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl-xL, cFLIP, XIAP, c-IAP1), caspase activation pathway (caspase-8, 3, 9), tumor suppressor pathway (p53, p21) death receptor pathway (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, Akt, and AMPK). These interrelated pathways are activated by:
a) Caspase Activation
b) Induction of Death Receptors
c) Fas Receptor Aggregation
d) Induction of p53/p21 Pathway
e) Release of Apoptosis-Inducing Factor
f) Cell Cycle Regulation
g) Inhibition of PI3K-AKT Activation
h) Inhibition of mTOR
i) Down-Regulation of Androgen Receptors
j) Inhibition of Growth Factors and their Receptors
k) Inhibition of AMP-Activated Protein Kinase (AMPK)
l) Inhibition of COX2 and 5 LOX
m) Inhibition of Ornithine Decarboxylase
n) Inhibition of Acidic Sphingomyelinase
o) Inhibition of Phospholipase D
p) Activation of Thioredoxin Reductase
q) Inhibition of STAT3 Activation
r) Activation of c-Jun Kinase
s) Induction of DNA Fragmentation
t) Direct DNA Damage
u) Intracellular [Ca (2±)](i) Depletion
v) Mitochondrial Activation
w) Binding and Inhibition of Glyoxalase
x) Suppression of Antiapoptotic Proteins
y) Binding to Microtubules
z) Proteasome Activation
aa) Pro- and Antioxidant Mechanisms
bb) Autophagy
cc) Inhibition of NF-κB
dd) Inhibition of Wnt/beta-catenin Signaling
ee) Activation of Nrf2
ff) Inhibition of hTERT

Jayraj Ravindran, Sahdeo Prasad and Bharat Aggarwal from Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Cente, in their Paper Curcumin and Cancer Cells: How many ways can curry kill tumor cells selectively? concludes by saying that due to its multiple pathways to inhibiting and killing, cancer cells are unable to develop resistance to turmeric and curcumin.

Curcumin has the most evidence-based literature supporting its use against cancer of any nutrient. Curcumin has the ability to modulate genetic activity and expression—both by destroying cancer cells and by promoting healthy cell function. It also promotes anti-angiogenesis, meaning it helps prevent the development of additional blood supply necessary for cancer cell growth. As for its effect on molecular pathways, curcumin can affect more than 100 of them, once it gets into the cell. Some of the actions of Curcumin in non-medical terms: Inhibit the proliferation of tumor cells, Inhibit the synthesis of a protein instrumental in tumor formation, Inhibit the transformation of cells from normal to tumor, Help your body destroy mutated cancer cells so they cannot spread throughout your body, Help prevent the development of additional blood supply necessary for cancer cell growth.

There is so much incredible research about curcumin that it can fill a hundred pages easily of this blog post. I am citing only this recent study because it proves curcumin efficacy against the heart of cancer as per our new understanding of CSCs. In a recent study published in Cancer Letters it was observed that curcumin was a potent cancer fighter on its own and safe as an adjuvant to chemotherapy. Chemotherapy was effective in killing relatively benign 'daughter cells' of a tumor whereas curcumin attacked the relatively chemotherapy resistant cancer stem cells 'mother cells' at the heart of the tumor. So chemo may seem to reduce the volume of the tumor if administered alone but it left smaller but far more dangerous treatment resistant tumor which eventually killed the patient. This new revelation about cancer cells from these recent studies is shaking up the old beliefs. It seems there are only few mother stem cells CSCs (1%) at the heart of a tumor which possess the multiplication and mutagenic ability - majority of the cancer cells do not. Conventional Chemo kills these benign daughter cells and therefore we are puzzled when the CSCs rebound later to an aggressive and lethal cancer that eventually quickly kills the patient with a post chemo injured immune system. The conclusion of this study: Curcumin, as well as its modified forms (analogues or nanoparticle-encapsulated formulations), has shown great potential to inhibit CSCs in several types of cancer both in cell cultures and in mouse models, including glioma, breast, colorectal, pancreatic, brain, and esophageal cancers. Some analogues (e.g., CDF) and formulations (e.g., nanotechnology-based formulation) have exhibited improved efficacy against CSC-like cells and greater growth-inhibitory capacity in tumors. It is promising to evaluate curcumin and its modified forms in other types of CSCs.

For unknown reasons curcumin only kills cancer cells and does not kill healthy cells putting to shame chemo which does not differentiate. This seems to be a must therapy for all cancer patients along with whatever other treatment they are taking. But one of the biggest challenges to keep in mind is that turmeric and curcumin (an extract of turmeric) have low bioavailability much below the potency required to kill CSCs. A 95% concentration curcumin capsule will provide only 1% as bioavailable (boiling the contents of the capsule before consuming increases absorption to 12%). One can also remedy this by taking curcumin with piperine (extract of black pepper) which increases the bioavailability by 2,000% or turmeric should be consumed with healthy fats - it is otherwise difficult to absorb in the gut but is fat soluble so taken with healthy fats it is better absorbed. Quercetin is a plant flavonoid that inhibits the enzyme that deactivates curcumin so take it along with a Quercetin supplement. Turmeric is one of the most potent natural compounds in the world with 600 tested benefits! including anti-inflammatory, anti-oxidant, anti-viral, anti-bacterial, etc. Many more are being discovered every day.

2. GEDUNIN: Hsp90 is a heat shock protein which protects our cells during heat and stress based biological events. Cancer cells hijack this chaperone protein to protect itself while multiplying and mutating endlessly. Inactivation of he Hsp90 machinery would render cancer cells vulnerable and eventually lead to their death (apoptosis), No wonder a lot of cancer research is aimed at inactivating Hsp90 selectively in the cancer environment. The challenge with all the experiments so far has been that inhibiting Hsp90 has led to overexpression of other proteins like Hsp70 and Hsp27 which are anti-apoptotic negating the gains or worsening further. Gary E Brandt from the University of Kansas along with colleagues have been doing some interesting research work finding inhibitors of Hsp90. In 2008 he concluded that Gedunin an extract of the Neem tree of India inhibits Hsp90 without the negating overexpression of other proteins but he could not determine the mode of action. He also concluded that synthetic or semi synthetic derivatives of Gedunin were not at all effective as the natural extract itself.
Cancer Killer from Neem Tree
Chaitanya A Patwardhan under Ahmed Chadli of the Cancer Research Center, Molecular Chaperones Program, Georgia Regents University along with fellow collaborators discovered the method by which Gedunin was effective. One of the co-chaperones of Hsp90 is called p23. Gedunin binds to p23 thereby inactivating it. The inactivation of p23 in turn renders Hsp90 inactive. Which in turn leads to apoptosis of cancer cells. In lab experiments Gedunin has shown clearing certain hormonal cancers in a weeks time. Subject to further tests Gedunin can become a great therapeutic candidate in the war against cancer. Research must also be done to identify the best form of Gedunin like Deoxygedunin a more stable form and the bioavailability of it to ensure clearance of all cancer cells. Good news is that it can be orally taken. Hormonal cancer patients like breast, endometrium, ovary, prostate, testis, thyroid and osteosarcoma should speak with their doctors about integrating Deoxygedunin into their therapy. I can't explain why but my favourite Natural compound against cancer is Gedunin on its own or combined with other compounds found in Neem or with other Natural compounds - I feel that if extracted correctly, if made amply bioavailable at the cellular level it can wipe out all hormonal cancer cells in a few days.

3. SUPER COCKTAIL: This is an important discovery as it demonstrates the power of synergy in using natural compounds. The combination of 6 powerful natural compounds killed 100% of all breast cancer cells while not harming healthy cells in vitro. Individually their effect was muted but in combination they proved synergistically powerful enough to kill ALL cancer cells in an experiment conducted by Dr. Madhwa Raj and colleagues of LSU Health and Science Center, New Orleans and its Stanley C Scott Cancer Center. Let me list out the super six:
a. Curcumin
b. Indol-3-Carbinol
c. Isoflavone (Genistein)
d. Spirulina extract combined with Selenium
e. Resveratrol
f. Quercetin

4. KILLING CANCER STEM CELLS: The new startling discovery about cancer biology which disclosed to us the dark heart of the cancer tumor holding the Cancer Stem Cells CSCs which as explained above do all the damage. CSCs have proven elusive to conventional chemo therapies. Scientists are now discovering that it is only Natural Compounds which have shown ability in various experiments to kill CSCs. 
These natural killers so far discovered that attack CSCs in different pathways are:
a. Curcumin
b. Salinomycin
c. Sulforaphanes (extract from cruciferous vegetables like Broccoli)
d. BXL0124 (a novel analogue of vitamin D)
e. 6-Shogaol
f. Phenethyl isothiocyanate (PEITC)

5. 6-SHOGAOL (Extract of GINGER): 10,000 times more effective than chemo at killing CSCs as discovered in a recent study published in highly reputed PLoS Journal. The chemical, known as 6-shogaol, is produced when ginger roots are dried or cooked.

The researchers found that 6-shogaol is active against cancer stem cells at concentrations that are harmless to healthy cells. The researchers found that 6-shogaol targets breast cancer stem cells along several different pathways, including reducing the expression of surface markers, altering the cell cycle to increase the rate of cell death, inhibiting tumor formation, directly inducing programmed cell death, and flat-out poisoning cancer stem cells (cytotoxicity). The researchers then compared the cytotoxicity of 6-shogaol against human breast cancer stem cells with that of the widely used chemotherapy drug taxol. They found that while taxol did show cytotoxicity in a one-dimensional laboratory model of cancer ("monolayer"), it showed almost no effect in the three-dimensional ("spheroid") model that is now believed to be a more accurate model of real-world cancer tumors. 6-shogaol, however, was effective in both the monolayer and spheroid models. The researchers then increased the taxol concentration by 10,000 times, but it still showed no effectiveness in spheroid model. "Taxol, even though was highly active in monolayer cells, did not show activity against the spheroids even at 10,000 fold higher concentration compared to 6-shogaol," the researchers wrote.
Separately A study by the Georgia State University has found that ginger can decrease the size of a prostate tumour by 56%.

6. BEC5 (Eggplant Extract): One of the biggest success stories of Nature derived absolute cure of cancer - skin cancer - seems to have gone unnoticed by most of the world. The brilliant, unassuming scientist Dr. Bill Cham who deserves worldwide recognition for his incredible breakthrough in a major diseases like cancer. The discovery of BEC5 - Solasidine Glycoside -extracted from eggplant and Devil's Apple - was pointed out to us by cows! Cows stricken by eye cancer in Queensland, Australia cured it by rubbing on a plant called Devil's Apple. This was brought to the attention of Dr. Cham and he toiled away to develop the best available cure for malignant and non malignant skin cancers.
Dr. Bill Cham
Stage III trials have confirmed that 8 weeks of topical application of BEC5 cream cured 78% of the skin cancer and Dr. Cham discovered that 12 weeks of topical use twice a day cured it 100%! without leaving any scar or harming the surrounding normal skin. tens of thousands of patients have benefited from this already with no remission even after 5 and 10 years after treatment. Now BEC is in trials for internal cancers and early results are promising.

7. SALINOMYCIN: One of the more exciting biochemicals which has shown potent anti cancer activity including for CSCs in in vivo human clinical trials.  Salinomycin is made by a strain of  streptomyces albus. Streptomyces is a form of bacteria, usually found in soil. Its a naturally occurring antibiotic. Promising results from preclinical trials in human xenograft mice and a few clinical pilot studies reveal that salinomycin is able to effectively eliminate CSCs and to induce partial clinical regression of heavily pretreated and therapy-resistant cancers.
Salinomycin can kill CSCs
The ability of salinomycin to kill both CSCs and therapy-resistant cancer cells may define the compound as a novel and an effective anticancer drug. Importantly, salinomycin is not only able to kill CSCs, but also regular tumor cells and highly indolent tumor cells displaying resistance to cytotoxic drugs, radiation, and induction of apoptosis  hence salinomycin can be regarded as a triple-edged sword against cancer. This is what is reported in Wikipedia for it: Salinomycin has been shown by Piyush Gupta et al. of the Massachusetts Institute of Technology and the Broad Institute to kill breast cancer stem cells in mice at least 100 times more effectively than the anti-cancer drug paclitaxel. The study screened 16,000 different chemical compounds and found that only a small subset, including salinomycin and etoposide, targeted cancer stem cells responsible for metastasis and relapse. In one recent peer reviewed study investigations revealed that salinomycin effect on cell cycle progression using OVCAR-8 ovarian cancer cell line and multidrug-resistant NCI/ADR-RES and DXR cell lines that are derived from OVCAR-8. Parental OVCAR-8 cells are sensitive to several anticancer drugs, but NCI/ADR-RES and DXR cells are resistant to several anticancer drugs. However, salinomycin caused cell growth inhibition and apoptosis via cell cycle arrest at G1 in all three cell lines! Their sdata indicate that salinomycin induces cell cycle arrest and apoptosis via downregulation or inactivation of cell cycle-associated oncogenes, such as Stat3, cyclin D1, and Skp2, regardless of multidrug resistance. Study was conducted by KH Koo at National Cancer Centre, Korea.
Another Study by Florian Kopp and others reports "Our findings clearly show that salinomycin can strongly inhibit cancer cell migration independent of the induction of cell death. We furthermore demonstrate for the first time that salinomycin treatment reduces metastasis formation in vivo, strengthening its role as promising anti-cancer therapeutic". In another trial by Zhao P of University of Utah iTEP nanoparticle-delivered salinomycin displays an enhanced toxicity to cancer stem cells in orthotopic breast tumors. The amazing thing about this super drug is that compared to conventional chemo and radio therapies it has shown few side effects. In a documented human cancer patient case study intravenous salinomycin therapy resulted in minor acute side effects, including tachycardia and mild tremor for 30–60 min. after administration but lacked severe and long-term side effects observed with conventional chemotherapeutic drugs. With 12 cycles of salinomycin therapy greater than 85% of the cancer cells had undergone apoptosis. Similar results of salinomycin-induced partial tumor and metastasis regression were obtained in three other patients with metastatic breast cancer, one patient with metastatic ovarian cancer, and one patient with metastatic head and neck squamous cell carcinoma.

8. SALVESTROLS: Salvestrols are naturally occurring extracts of fruits and vegetables which are metabolized by the CYP1B1 enzyme in cancer cells. While harmless to normal cells, these metabolites will kill cancer cells in a process called apoptosis. The discovery of Salvestrols was due to the collaboration between two CYP 450 enzyme experts,  Gerald Potter PhD a medicinal chemist,and Danny Burke PhD.
Discovered and sold Abiraterone Prostrate Cancer decimater smart bomb for US$ 1 billion
According to the Dana-Farber Cancer Institute CYP1B1 is found inside cancerous cells of tumours within the bladder, brain, breast, colon, kidney, liver, lung, oesophagus, ovary, skin, small intestine, stomach and uterus and is considered to be a tumour marker enzyme since it is virtually exclusive to cancer cells. So, CYP1B1 can be thought of as a Trojan Horse inside cancer cells, which merely has to be provided with Salvestrols in the diet in order to unleash a stream of chemical agents that are deadly to cancer cells. In other words, the presence of CYP1B1 in cancer cells seems to have provided cancer cells with the seeds of their own destruction.

So the logic sounds strong but the sad part is the lack of validation achieved in clinical trials yet. I am listing this only because of two reasons - The very distinguished career, awards and achievements of Dr. Gerald Potter and second because of the multitude of actual patient case studies published in reputed medical journals. Dosage (of Salvestrols Platinum)  is reported to be in the 12,000 point range for cancers that have spread along with biotin, niacin, vitamin C and others. Chloroquine is also supposed to work well with Salvestrols but chloroquine must never ever be taken while one is on chemotherapy as it can cause severe kidney injury amongst other things. Salvestrols on their own have been allowed by many oncologists during chemotherapy as they do not show any contraindications probably due to their natural origin.

9. CRUCIFEROUS COMPOUNDS: Cruciferous vegetables like brocolli, kale, brussels sprouts, arugula, bokchoy, cabbage and cauliflower have not one but many powerful anti cancer compounds like Indole-3-Carbinol, DIM, Sufurophanes, Crambene and PEITC. Scientific observational studies have shown that eating cruciferous vegetables protects against cancer – here are a few examples:
Twenty-eight servings of vegetables per week decreased prostate cancer risk by 33%, but just 3 servings of cruciferous vegetables per week decreased prostate cancer risk by 41%.
One or more servings of cabbage per week reduced risk of pancreatic cancer by 38%.
One serving per day of cruciferous vegetables reduced the risk of breast cancer by over 50%

These powerful compounds work both as potent cancer preventives and cancer fighters. Their actions are multiple. Some things to keep in mind to get best results: have cruciferous veggies with yogurt. Do not over cook them, I3C is unstable but its metabolite DIM is not - so take I3C supplement with a DIM supplement and also with Crambene. Some of these compounds work better with vitamin D. One example of cruciferous nutrients less known  is:
PEITC PHENETHYL ISOTHIOCYANATE: This chemical is produced from the reaction of a compound and an enzyme that occur in cruciferous vegetables, such as broccoli and cabbage. This reaction actually takes place simply when the vegetables are chewed, which means that eating cruciferous vegetables causes the human body to be exposed to PEITC. According to a May 2015 press release by researchers from the South Dakota State University Department of Health and Nutritional Sciences, PEITC has been successful at killing cervical cancer stem cells. The concentrations used in the study are actually achievable simply from a diet rich in cruciferous vegetables, the researchers said. The vegetables highest in PEITC potential are watercress and land cress. This research suggests that PEITC, and possibly even a diet rich in cruciferous vegetables, could assist in the prevention of or recovery from cancer.
Image result for PEITC cancer
PEITC preventing metastasis in lung cancer

One of the important actions of cruciferous veggie compounds is balancing hormones especially estrogen. They convert the dangerous forms of estrogen to protective forms thereby preventing cancer from forming.
For prevention and regression of hormonal cancers adding cruciferous veggies and supplements should be a must. My close relative was diagnosed with Fibroids and was looking at a debilitating surgery that would remove a lot of her womanhood. She tried concentrated supplement containing all the potent compounds found in cruciferous veggies and a miracle happened on pre-surgery visit to her gynac she was told that the Fibroids had disappeared much to the amazement of her doctor. So I have personally observed the benefit in a real life situation.

10. APIGENIN: A flavonoid found in many fruits. Apigenin has been shown to possess anti-mutagenic properties in a setting of nitropyrene-induced genotoxicity in Chinese hamster ovary cells. Apigenin has also been shown to inhibit benzo[a]pyrene and 2-aminoanthracene-induced bacterial mutagenesis.  apigenin has been shown to increase the intracellular concentration of glutathione, enhancing the endogenous defense against oxidative stress. n another study, apigenin treatment resulted in suppression of tumor necrosis factor (TNF) α-induced Nuclear Factor (NF)-κB activation in human umbilical vein endothelial cells. Apigenin treatment has been shown to decrease the levels of phosphorylated EGFR tyrosine kinase and of other MAPK and their nuclear substrate c-myc, which causes apoptosis in anaplastic thyroid cancer cells. apigenin has been shown to inhibit the expression of casein kinase (CK)-2 in both human prostate and breast cancer cells.
Celery source of Apigenin
Apigenin has also been shown to induce WAF1/p21 levels resulting in cell cycle arrest and apoptosis in androgen-responsive human prostate cancer, LNCaP cells and androgen-refractory DU145 cells. In vivo studies have also shown that apigenin inhibits melanoma lung metastases by impairing interaction of tumor cells with endothelium. Apigenin has also been shown to inhibit the expression of HIF-1α and VEGF via the PI3K/Akt/p70S6K1 and HDM2/p53 pathways in human ovarian cancer cells. Oral administration of apigenin was shown to suppresses prostate and breast cancer cell growth through estrogen receptor β1. Studies imply that apigenin may have the potential to inhibit hormone-related cancers as well. Studies have demonstrated anti-proliferative effects of apigenin on human breast cancer cell lines with different levels of HER2/neu expression. Apigenin exhibited potent growth inhibitory activity in HER2/neu over-expressing breast cancer cells. Induction of apoptosis was also observed in HER2/neu over-expressing breast cancer cells in a dose- and time- dependent manner after apigenin treatment. The first report about apigenin in human cervical carcinoma HeLa cells demonstrated apigenin inhibited the growth through an apoptotic pathway.Findings indicate that the induction of cell-cycle arrest by five of seven tested apigenin analogs and the additive induction by the combination of flavonoids at low doses cooperatively protect against colorectal cancer through conjoint blocking of cell-cycle progression. Apigenin was shown to be markedly more effective than other tested flavonoids in inducing apoptosis in human leukemia cells. 
Swiss Chard
Swiss Chard contains apigenin flavonoids, namely vitexin, vitexin-2-O-rhamnoside and vitexin-2-O-xyloside, which show antiproliferative activity on cancer cell lines
 The effects of apigenin on lung cancer cells were evaluated, apigenin inhibited A549 lung cancer cell proliferation and vascular endothelial growth factor (VEGF) transcriptional activation in a dose-dependent manner. Among the flavonoids tested, apigenin was the most potent inhibitor of the proliferation of human thyroid carcinoma cell lines. Exposure of human gastric carcinoma SGC-7901 cells to apigenin resulted in dose-dependent inhibition of the growth and clone formation of SGC-7901 cells by inducing apoptosis. Apigenin was also found to have inhibitory and apoptotic action on Liver cancer cells through various paths. Apigenin treatment has been shown to result in inhibition of colony-forming ability and survival, and induction of apoptosis in human neuroblastoma cells. The role of Apigenin in cancer prevention and therapy has been well documented by Sanjay Shukla and Sanjay Gupta from Department of Urology & Nutrition, Case Western Reserve University in their Paper Apigenin: A promisng molecule for cancer prevention. Overall it surely has shown effective in chemoprevention but therapeutic potency needs further evaluation. Also Dosage would be very important as in one sole in vitro test Apigenin was shown to be toxic to red blood cells.

11. SANGRE DE GRADO: This amazing compound has an unbelievable antioxidant count of 2,987.11 nmol/100g of antioxidants highest amongst 3,100 food items ranked in study conducted in Norway. As a comparison blueberry a favorite anti oxidant has count of 1.25 nmol/100g. So SDG is almost 3,000% more potent than blueberries.
Sangre de Grado Tree
The most powerful antioxidant in the world - The Sap from the tree
The Sangre de Drago tree (Croton lechleri) is a tall, narrow tree that grows primarily in the Upper Amazon region of Peru, Ecuador, and Colombia. Sangre de Drago has 3 especially exciting cancer-slaying capacities: it can kill cancer cells, prevent tumor growth, and stop cell mutation.
The blood red Sap
In 2002, the Journal of Ethnopharmacology published a study conducted at Albany Medical College. The researchers there found that Sangre de Drago could induce apoptosis or cell death. Unfortunately these tests were in vitro - a long way from proving any efficacy in humans. Despite this I list this here because of its incredible antioxidant potency probably and by far the highest in the world amongst natural products. As we know that antioxidants can protect us from many causes of cancer in our body. I hope that very soon further research is done on SDG and that it will amaze us with its anti cancer therapeutic capabilities as well.

12. ROSEMARY: Has many compounds and extracts which have proven potent against cancers. Rosemary contains the active compounds alpha-pinene, beta-pinene and 1,8-cineole and powerful extracts like carnosic acid, rosemarinic acid, carnosol and SFRE.
Rosemary plant can be grown year round

The essential oil of the common herb rosemary (Rosmarinus officinalis) was shown in this lab study to potently reduce the viability of two types of human ovarian cancer cells: (SKOV-3) by up to 94% and HO-8910 by up to 90%. In addition, the essential oil also reduced the viability of liver cancer cells (Bel-7402) by 90%, all after 48 hours of treatment. Another result of experiments with carnosol and carnosic acid: Rosemary extract, carnosol and carnosic acid, increased apoptosis, decreased viability in colon cancer cell lines. Rosemary extract, carnosol and carnosic acid significantly upregulated the expression of Nrf2 and ERK. Rosemary extract also effectively suppressed tumor growth in a xenograft tumor model without affecting body weight. In experiments done for prostrate cancer findings suggest that these polyphenols target multiple signaling pathways involved in cell cycle modulation and apoptosis. Essentially both diterpenes carnosol and cornosic acid inhibit cancer by promoting apoptosis and inhibiting the critical PI3K/Akt signaling pathway which is an important regulator of tumor cell survival.

13. LYCOPENE: Is a pigment that helps give red fruits and vegetables their color. It is most abundantly found on the skin of tomatoes. Cooking tomatoes multiplies the available lycopene. Otherwise getting sufficient lycopene in our bloodstream to have potent cancer protective and cancer therapeutic potency is quite difficult requiring is to eat 3 dozen tomatoes at a time.

There is a patented pill that has found a way to upregulate the amount of lycopene absorbed into our bloodstream. Lycopene scavenges free radicals to prevent cancers. Scientific studies show that lycopene helps prevent prostate, lung, and stomach cancers.
There is also scientific evidence that cancers of the pancreas, colon and rectum, esophagus, oral cavity, breast, and cervix could be reduced with increased lycopene intake. Added bonus is its ability to mitigate atherosclerosis and blood pressure.

14. BERBERINE: Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. It is found in Oregon grape, Tree turmeric, Barberry, Goldenseal and others. Its use in ancient times is found both in traditional Chinese medicines and Ayurveda. It has shown many benefits which will be listed in my forthcoming blog post on anti aging naturals. Fortunately there have been many studies done for Berberines anti cancer abilities including animal studies.

As on Wikipedia it seems to suppress the growth of a wide variety of tumor cells, including breast cancer, leukemia, melanoma, epidermoid carcinoma, hepatoma, pancreatic cancer, oral carcinoma, tongue carcinoma, glioblastoma, prostate carcinoma and gastric carcinoma. Animal studies have shown that berberine can suppress chemical-induced carcinogenesis, clastogenesis, tumor promotion, tumor invasion, prostate cancer, neuroblastoma, and leukemia. Dr. Bran D Lawenda on his quite useful blog Integrative Oncology Essentials lists what Berberine does against cancer: It slows cancer growth and causes cancer cell death through a variety of mechanisms: tumor cell apoptosis and cell cycle arrest, inhibits blood vessel growth to tumors, inhibition of tumor cellular invasion and metastases (spread), etc. One of the main anti-cancer targets that is inhibited by berberine is NF-kappaB. NF-kappa B is one of the most important proteins in our cells, acting as a key switch in the development and progression of inflammation and cancer. Cancer (and precancerous cells) often have a permanently activated NF-kappa B, which keeps the cells proliferating and prevents them from dying (apoptosis). Chronic inflammation can also be a result of activated NF-kappa B, and we know that chronic inflammation can lead to cancer growth. Additionally, berberine is a radio-sensitizer of tumor cells, but not of normal cells (in fact, it may protect normal cells.) Therefore, berberine may make radiation therapy more effective. 
Berberine also inhibits the tendency of cancer cells to become drug resistant over time by inhibiting the cellular membrane proteins that pump drugs out of the cell. When berberine is taken with numerous chemotherapy drugs, studies have shown that they work synergistically against cancer cells.
Combination of Berberine with Curcumin have shown some spectacular results in studies showing above 99% inhibition in A549, Hep-G2, MCF-7, Jurkat, and K562 cancer cell lines. Another study concluded their data suggest use of berberine and curcumin as adjunct therapeutics to overcome chemoresistance during treatment of gastric malignancies.
The bark of the rhizome of Oregon Grapes is one of the sources of Berberine

As with other promising anti-cancer plant compounds (i.e. green tea, turmeric, etc.), there are data suggesting that using the whole plant extract (Coptidis rhizoma or “huanglian”) may be more effective than simply taking berberine, alone. This is potentially due to synergistic effects of the many known and unknown anti-cancer compounds in the whole plant. He has mentioned a dose of 500 mg 2-3 times a day. While taking Berberine one must take precautions about its Metformin like efficacy in controlling diabetes. If you are already taking medicine for controlling blood sugar then you must ensure that combining that with Berbeine does not cause low sugar. Another thing to keep in mind is that taking berberine along with Sylimarin increases its bioavailability. It is also found that Melatonin enhances the atitumor activity of berberine.

15. FUCOIDAN AND AHCC: Fucoidan is a valuable substance that is obtained from the sliminess of most brown seaweeds. Fucoidan is considered to be a polysaccharide. It was discovered in 1913 by Professor Johann Kylin in SwedenAHCC is a remarkable natural compound that is made from the roots of Japanese medicinal mushrooms. During the past few years it is gaining use as an immune modulator and chemotherapeutic agent. AHCC is the most popular immune-supplement in Japan. There are hundreds of scientific papers showing the benefits of medicinal mushrooms in cancer and in immunity. In the case of AHCC there are more than 20 human clinical studies and it has been used in over 1000 clinics. AHCC works by modulating the immune system so that the body can:
Increase the production and activity of immune cells to stimulate the suppressed immune function.
Protect itself from the side effects of chemotherapy such as nausea and hair loss.
It can enhance the liver function to increase survival rate and better quality of life.
Unlike other medicinal mushrooms AHCC seems to modulate our immune system essentially “training” the immune cells to respond to pathogens, toxins, cancerous cells, and other dangers.
Recommended Reading
Hundreds of Studies have proven the plant compound Fucoidan to kill cancer cells and protect against radiation. 
For years scientists couldn’t really figure out why people on a small island off of Japan hardly ever suffered from cancer – until they stumbled onto a curious fetish the Okinawans had for a seaweed delicacy called Kombu (Mozuku) - there is a long chain carbohydrate in this seaweed called Fucoidan that has proven to fight cancer. It seems Fucoidan is lethal to certain types of cancerous cells. There are 600 peer reviewed studies that have proven its various efficacies against cancer. Fucoidan works by causing cancer cell apoptosis (causing death of cancer cells), cancer cell angiogenesis suppression (suppressing the blood vessels supporting the tumor) and boosting multiple immune mechanisms mainly via our intestinal flora. It has also been proven radioprotective. There is a book by Dr. Susana Trujillo about the synergy of Fucoidan and AHCC.

16. PTEROSTILBENE, HPSB AND RESVERATROL: Both the stilbenes one found in blueberries and one in red grapes have shown anti cancer activity in hundreds of peer reviewed studies and in vivo. One study has also shown a synergistic benefit but they have a difference in bioavailability that puts Pterostilbene ahead. Resveratrol is rapidly cleaned out by the liver while pterostilbene is allowed to continue on in the blood stream and eventually localize in the areas of need in the body.
Blueberries a source of Pterostilbene
A recent paper has demonstrated that when administered orally, Pterostilbene shows 95% bioavailability while resveratrol only has  20% bioavailability. Additionally, pterostilbene’s lower total body clearance rates suggest extensive tissue distribution. In a study by Dr. Wang it was concluded that pterostilbene could markedly inhibit the growth of two independent breast cancer cell lines. Both apoptosis and cell cycle arrest as well as the inhibition of wnt singling was induced by pterostilbene. Interestingly, pterostilbene induced autophagy and blockage of autophagy augmented pterostilbene-induced growth inhibition, suggesting that the combination of autophagy inhibitors with pterostilbene and other therapeutics such as endocrine drugs could serve as a new and promising strategy for the treatment of breast cancer cell. In vitro models have shown that pterostilbene inhibits cancer growth through alteration of the cell cycle, induction of apoptosis, and inhibition of metastasis. In vivo, pterostilbene inhibits tumorigenesis and metastasis with negligible toxicity. Pterostilbene has also been shown to be effective as an inducer of antioxidant capacity in multiple cancer cell lines that may facilitate its function as an anticarcinogenic compound. Additionally, preliminary studies show that pterostilbene exhibits much greater bioavailability compared with other stilbene compounds. 3′-hydroxypterostilbene (HPSB), a natural pterostilbene analogue, was more potent than pterostilbene against the growth of human cancer cells. HPSB effectively inhibited the growth of human colon cancer cells by inducing apoptosis and autophagy. Significant therapeutic effects were demonstrated in vivo by treating nude mice bearing COLO 205 tumor xenografts with HPSB. A study led by Salvador Mena in Plos One Journal showed the mecahnism by which pterostilbene acts against cancer:Pterostilbene promotes cancer cell death via a mechanism involving lysosomal membrane permeabilization. Different grades of susceptibility were observed among the different cancer cells depending on their lysosomal heat shock protein 70 (HSP70) content, a known stabilizer of lysosomal membranes. A375 melanoma and A549 lung cancer cells with low levels of HSP70 showed high susceptibility to pterostilbene, whereas HT29 colon and MCF7 breast cancer cells with higher levels of HSP70 were more resistant. Inhibition of HSP70 expression increased susceptibility of HT29 colon and MCF7 breast cancer cells to pterostilbene. Our data indicate that lysosomal membrane permeabilization is the main cell death pathway triggered by pterostilbene.

17. HONEY, ROYAL JELLY, PROPOLIS AND BEE POLLEN: A fantastic review by Dr. Sarfaraz Ahmed and Othman of Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia concluded that evidence is growing that honey may have the potential to be anticancer agent through several mechanisms. Studies have shown it has the following actions on cancer;
Its Apoptotic
Its Antiproliferative
It Effects Tumor Necrosis Factor (TNF)
Its Anti-Inflammatory and Immunomodulatory
Its Antioxidant
Its Antimutagenic
Estrogen Modelator
In an article "Honey a Powerful Anicancer Agent" Sayer Ji says that Indeed, a recent study published in the journal Molecules looked at the role of honey in positively impacting the development and progression of tumors or cancers. Some honeys – such as Tualang honey – exhibit the property of selective cytotoxicity, meaning they target cancer cells by inducing programmed cell death while leaving non-cancerous cells unharmed. Another recent study compared the effect of Tualang honey with that of the pharmaceutical tamoxifen (an estrogen receptor antagonist) in two breast cancer cell lines (MCF-7 and MDA-MB-231). The study found that the anti-cancer effect of tualang honey on breast cancer cells was comparable to that of tamoxifen, a multi-billion dollar blockbuster drug. This is all the more remarkable, considering that Tamoxifen is classified by the World Health Organization and the American Cancer Society to be a human carcinogen, and is technically a xenobiotic chemical – inherently toxic and biologically alien to human physiology proving honey to be better than chimotherapy. According to the study, animal research has established honey’s significant anti-cancer properties, specifically in regard to inhibiting metastasis (invasiveness). Honey Kills A Wide Range of Cancers:
Liver Cancer: Gelam honey has been found to kill liver cancer cells, exhibiting selective cytotoxicity, anti-angiogenic, cytotoxic, and anti-proliferative properties, in both cell and animal research.
Colorectal Cancer: gelam and nenas monofloral honeys exhibit anti-cancer properites in colorectal cell lines. Prostate Cancer: Greek honeys (thyme, pine and fir honey) have been found to exhibit anti-proliferative properties.
Other Forms of Cancer: There has been a battery of studies on the anti-cancer properties of honey, focusing on the following types: a) bladder b) endometrial c) renal cell carcinoma d) skin cancer cells e) cervical f) non-small cell lung cancer g) mouth cancer h) bone cancer (osteosarcoma)
ROYAL JELLY: is a milky substance secreted from the glands in the hypopharynx of worker bees.  It isn’t honey or bee pollen but those who are allergic to bees should not use royal jelly. Worker bees feed royal jelly to larvae and adult queen bees.  In fact, it is the queen’s principal food throughout her lifetime, enabling her to lay 2,000 eggs a day and live for 5 to 8 years.  The queen bee lives 40 times longer than worker bees and researchers are discovering that royal jelly might hold the key to their longevity, strength and size says Ty Bollinger in a poast called Can Royal Jelly Cure Cancer? It contains an abundance of health benefits that meet specific needs for cancer patients, keeping them strong and healthy before, during and after traditional treatments. It helps cancer patient by Immune System: Royal jelly is a natural immune system modulator and booster + Blood Sugar Controls:controls blood serum sugar levels with its insulin-like activity + Anti-Inflammatory:suppresses pro-inflammatory cytokines, lowers your risk of cancer and controls inflammation during treatment + Antioxidant:contains concentrated levels of several antioxidants + Liver Protection: dead tumor tissue makes the liver toxic and can lead to liver cancer.  The liver-protective compounds in royal jelly help to flush these toxins + Protection from Breast Cancer:nhibited the growth promoting effects of BPA on breast cancer MCF-7 cells, even though it did not affect the proliferation of cells in the absence of BPA. +
ccording to a study published in a 2009 edition of the BMC Complementary and Alternative Medicine, royal jelly fights cancer by suppressing the blood supply to tumors + There are studies regarding royal jelly in treating leukemia + Several clinical tests have proven that royal jelly reduces the harmful effects of cisplatin (chemotherapy drug) on the kidneys and liver. Can it cure cancer is still up for speculation but there is no doubt that supplementation by cancer patient may lead to many benefits and that is the reason it features here.
PROPOLIS:  Propolis is the "caulk" honeybees use to patch holes in their hives. New research has revealed another exciting use for this seemingly miraculous substance, this time in the fight against cancer.In an article in Greenmedinfo Eleni Roumeliotou writes about Extreme Anticancer Potential of Propolis. One of the well-studied compounds of propolis is caffeic acid phenethyl ester, abbreviated as CAPE. CAPE has great medicinal properties, but its anti-cancer capacity is of particular interest. A study from the "Journal of Radiation Research" shows that just within 2 days after treatment with CAPE, 46% of lung cancer cells had been destroyed and the cancer growth was reduced by 60%. Three days after the treatment 67% of cancer cells were dead. A similar study published in the journal "Anticancer Drugs" in 2006 found that CAPE prevents colon cancer cells from multiplying and induces programmed cell death of the malignant cells without affecting healthy cells. These impressive results have been replicated in more types of cancer cells, such as breast, gastric, skin and pancreas cancer and glioma cells, a type of inoperable brain cancer. The available data show that CAPE can selectively stop the cell cycle and destroy cancer cells, prevent angiogenesis and block cancer growth. Luckily, it is not just CAPE having this impressive ability. The same anti-cancer properties are even more pronounced and superior in propolis as a whole food. In cells grown in a lab, even small doses of CAPE slowed the growth of tumor cells. And when low oral doses were given to mice with prostate tumors, tumor growth slowed by 50 percent! What's more, feeding CAPE to mice daily caused the tumors to stop growing, although they returned when the CAPE was removed from their diets. there are at least four studies on propolis' apoptotic properties, indicating that technically it is capable of directly killing cancer cells, including prostate cancer, melanoma and more. In 2009, propolis was found to suppress the growth of neurofibromatosis-associated tumors (tumors on nerve tissue) by blocking PAK1 signaling. Researchers noted: "Since more than 70% of human cancers such as breast and prostate cancers require the kinase PAK1 for their growth, it is quite possible that GPE [green propolis extract] could be potentially useful for the treatment of these cancers, as is Bio 30 [a CAPE-based propolis extract]." as quoted by Dr. Mercola. Perhaps the most exciting discovery about the healing effect of propolis and CAPE comes from a recent study published in the journal "Cancer Science and Therapy" in 2014, which shows that treatment with propolis can actually change the expression of DNA. Propolis and CAPE have a dramatic effect on specialized enzymes (called histone deacetylases), which are responsible for regulating the expression of DNA, preventing epigenetic modifications. Eleni adds that The scientific and commercial implications of these findings are so important that an international patent application on this finding was published in January, 2013 by the group, Omene C, O'Connor OA and Frenkel K. all cells have in their DNA specialized genes, called tumour suppressor genes, which are expected to be activated if a cell becomes cancerous and either promote healing or induce programmed cell death, if the genetic damages are beyond repair. These protective genes are usually deactivated in cancer cells, allowing them to bypass the security mechanisms built in the DNA. This is exactly where propolis acts; by restoring the functions of DNA, it re-activates the ability of the cell to fight off the malignancy and regulate its replication, therefore blocking tumour growth proving that CAPE and propolis are naturally occurring epigenetic therapeutic agents.

18. CAPSAICIN: A compound (vanilloid family of compounds) found in chlli peppers has been shown to selectively kill cancer cells. In a report filed in September 2015 says that capsaicin has been known to kill prostate cancer cells for about a decade. Researchers have moved closer to a way of using the molecule in cancer treatment by figuring out how it works, they report in a new study. A recent study in China found it can lower the risk of death from cancer, heart and respiratory diseases. In 2006, a study found that capsaicin can cause prostate cancer cells in mice to die while leaving healthy cells alone.
Worldwide, more than 1.1 million cases of prostate cancer (pictured under the microscope) were recorded in 2012, according to the World Cancer Research Fund. It accounted  for eight per cent of all new cancer cases
Prostrate Cancer under microscope
It caused 80 per cent of cancer cells to start the process leading to cell death, and had no side effects. It required, however, giving the mice a dose of the molecule equivalent to a 200-pound-man eating three to eight habanero peppers three times a week.
Researchers Dr Ashok Mishra and Dr Jitendriya Swain at the Indian Institute of Technology Madras found in a new study, published in The Journal of Physical Chemistry, that the molecule binds to the surface of cancer cells and affects the membrane that surrounds and protects it. By detecting how the molecule interacts with cell membranes, they hope to find better ways of delivering it when attempting to kill cancer cells. "The study showed that capsaicin lodges in the membranes near the surface," the researchers said in a press release. "Add enough of it, and the capsaicin essentially causes the membranes to come apart. With additional research, this insight could help lead to novel tools against cancer or other conditions." The news follows a study published last year which found eating chilli could also reduce the risk of developing bowel cancer. Researchers gave capsaicin to mice genetically prone to developing multiple tumours in their gastrointestinal tract. It triggered a pain receptor in the cells lining their intestines, setting off a reaction that reduced the risk of growing colorectal tumours. Scientists publishing their work in the Journal of Clinical Investigation found the treatment extended the lifespan of the mice by more than 30 per cent
Combining capsaicin with caffeine seems to improve its efficacy.

19. XANTHONES from MANGOSTEEN: An interesting study published in Current Molecular Medicine Dr. Shan T. and colleagues of Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi’an Jiaotong University concluded as follows: Xanthones, from the pericarp, whole fruit, heartwood, and leaf of mangosteen (Garcinia mangostana Linn., GML), are known to possess a wide spectrum of pharmacologic properties, including antioxidant, anti- tumor, anti-allergic, anti-inflammatory, anti-bacterial, anti-fungal, and anti-viral activities. The potential chemopreventive and chemotherapeutic activities of xanthones have been demonstrated in different stages of carcinogenesis (initiation, promotion, and progression) and are known to control cell division and growth, apoptosis, inflammation, and metastasis. Multiple lines of evidence from numerous in vitro and in vivo studies have confirmed that xanthones inhibit proliferation of a wide range of human tumor cell types by modulating various targets and signaling transduction pathways. Here we provide a concise and comprehensive review of preclinical data and assess the observed anticancer effects of xanthones, supporting its remarkable potential as an anticancer agent.

In another study Dr. Gongbo Li of Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago concluded: describing the anti-cancer activity and mechanisms of mangosteen polyphenolic xanthones including α-Mangostin against breast cancer and prostate cancer. So far, extracts and individual xanthones have been found to induce apoptosis and inhibit proliferation on cancer cells in vitro and in vivo. Based on the reported findings there is clear evidence that these polyphenols target multiple signaling pathways involved in cell cycle modulation and apoptosis.
It seems Xanthone-packed mangosteen juice is available online and in many local health food stores; you can also buy mangosteen extracts in capsule or tablet form. The customary dosage for the capsules and tablets is 500 milligrams by mouth twice a day; the usual dose for mangosteen juice is 30 milliliters a day.

20. SELENIUM: Is a trace mineral that has shown very potent cancer preventive action. One study shows aging individuals supplementing with 200 mcg per day of selenium saw their risk of dying from all cancers slashed by 50%! Unfortunately food sources of selenium are getting scarce due to poor soil quality. Organic foods though may contain selenium. Supplements seem to be an insurance to ensure that one is not deprived of its powerful anti-cancer activities. Kirk Stokel in Life Extension Magazine has written a very good article on selenium against cancer. I am quoting some of his key reportings. Selenium acts by multiple, complementary pathways to prevent cancers from developing.

This is known as pleitropy is significant because cancers all have multiple causes and mechanisms of their own. which readily overcome single targeted therapies. Studies have revealed that Selenium has 12 mechanisms of action against cells developing into cancer cells. New mechanisms are still being discovered. Large-scale epidemiologic studies have repeatedly demonstrated that populations with low selenium levels are at significantly increased risk for developing many different types of cancer. Multiple studies reveal that low selenium levels in the blood, hair, or nail clippings are associated with a two to threefold increase in overall cancer risk. For specific tumors such as thyroid cancer, the risk rises to nearly 8-fold. Selenium insufficiencies are now known to increase risk of cancers of the bladder, lung, stomach, esophagus, liver, prostrate and colorectal. But not all forms of selenium are the same. He has identified 3 forms and listed their benefits. The three forms of selenium most important in cancer prevention are sodium selenite, L-selenomethionine, and selenium-methyl L-selenocysteine. the three selenium compounds complement one another in the ways they affect your body's expression of important proteins involved in cancer prevention and suppression. In addition, all three selenium compounds induce cell death in various cancer types, but each compound is better at destroying some cancers than others. Data indicates why both the organic forms of selenium (L-selenomethionine and selenium-methyl L-selenocysteine), plus inorganic sodium selenite, are required to kill off all incipient cancer cells that might be developing in your body.

SODIUM SELENITE: Inorganic sodium selenite destroys cancer cells from a variety of cancers through a variety of mechanisms. One of its most intriguing anti-cancer mechanisms is the selective generation of toxic reactive oxygen species ROS and targeted destruction of mitochondria that exist in tumor cells but not in healthy tissue. Sodium selenite has been shown to increase the activity of the antioxidant enzyme glutathione peroxidase in healthy tissue, thereby conferring double protection. Sodium selenite enhances the repair of damaged DNA segments, reducing the risk of new cancer development. By enhancing immune system responsiveness, sodium selenite increases the likelihood that abnormal cancer cells will be destroyed. A vital mechanism of sodium selenite's action is to decrease a protein called Bcl-2, that is abnormally elevated in cancer cells, preventing their natural death by apoptosis. As a result, sodium selenite increases cancer cell death by apoptosis. Numerous human studies with sodium selenite support the use of this form of selenium as a possible adjunct therapy for cancer patients and for preventing new or recurring cases of cancer. In terms of prevention, sodium selenite supplementation reduced the occurrence of new cases of liver cancer by 50% in a large group of Chinese people living in a high-risk area for that cancer. This study provided patients with 500 mcg per day for 3 years.
L-SELENOMETHIONINE: In a famous 1996 study, Dr. Larry C. Clark of the University of Arizona it was discovered that the supplemented patients were significantly protected from death by all cancers a 50% reduction compared with controls!
SELENIUM-METHYL L-SELENOCYSTEINE: This form of selenium is attracting a lot of scientific studies recently. It is found in the ellium family -garlic and onions-grown in selenium rich soils. It is one of the most potent forms of selelnium known. Lab studies reveal many unique mechanisms against cancer for this form of selenium. Most intriguingly it restors proteins associated with normal circadian rhythms disruption of which has shown to lead to many cancers especially breast cancers. It normalizes levels of melatonin and estrogen related to aggressive breast cancers. Another action it has shown is angiogenesis. It also downregulates Bcl-2 which slows down apoptosis of cancer cells thereby accelerating cancer cell destruction.

21. MELATONIN: Continuing on the importance of using a pleiotropic against cancer as both work with multiple mecahnisms and try to outwit each other. Cancers would eat single mechanism treatments for breakfast growing a resistance very soon to it. Recent studies have confirmed that Melatonin is a surprisingly effective multitasking molecule. It also works quite well in conjunction with conventional and natural cancer therapies. Connie Strasheim has written a good article in Natural News. Listing its actions as follows: It inhibits cancer cell growth and proliferation; it destroys cancer cells, stops angiogenesis (new tumor blood vessel growth), and prevents harmful forms of estrogen from stimulating cancer cell growth. Melatonin functions to destroy cancer in multiple ways. First, because it is toxic to cancer cells, it induces apoptosis, or cancer cell auto-destruction, as well as directly kills cancer cells. It also slows tumor growth through a variety of mechanisms, such as by inhibiting epidermal growth factor receptors on cancer cells. Epidermal growth factors play an important role in cancer cell growth and proliferation, so blocking their receptors on cancer cells prevents them from carrying out these roles.

Melatonin also stimulates the immune system and increases the cancer-killing activity of macrophages, monocytes, natural killer cells, T-helper cells and eosinophils, all of which are involved in cancer cell destruction. She says that despite its success in clinical trials and in doctors' experiences with their patients, it has not been widely prescribed in conventional medicine, though its effects have proven to be superior to those of many chemotherapeutic drugs. Studies have revealed melatonin to be more effective for treating pancreatic and lung cancers than a drug commonly used to treat these types of cancers. What's more, this drug may cost more than $4,000 per month, while twenty milligrams of melatonin cost approximately $11 per month. Melatonin plays a critical role in the host defense system against cancer’s progression by activating the cytokine system, which exerts growth-inhibiting properties,and by stimulating the cytotoxic activity of macrophages and monocytes. Melatonin has been shown to be an inhibitor on breast cancer. Administration of supplemental melatonin has been shown to be beneficial even in the supportive care of advanced and end-stage cancer patients: it lessens tissue wasting and diminishes weight loss, fatigue, weakness, and depression; enhances immune function; improves wound healing and improves quality of life 
and survival rates. Furthermore, melatonin improves common symptoms found in both patients with advanced cancer and those undergoing chemotherapy; it counteracts anemia and lymphocytopenia, stimulates platelet production, enhances appetite and diminishes cancer pain (including bone pain) through its natural analgesic properties. These are substantial benefits considering that approximately half of all patients diagnosed with cancer die because of poor symptom management. Some of the conjunctions that have worked: low dose subcutaneous IL-2, with Leupron from prostrate cancer.
Montmorency Cherries a very rich source of Melatonin
 One very interesting way to take melatonin in its natural form is by drinking Montmorency cherry juice. According to Dr. Russell Reiter of University of Texas, Health Science Center, “We were surprised at how much melatonin was in cherries, specifically the Montmorency variety.” Melatonin deserves a lot more research in labs then has been done so far.

22. GREEN TEA AND EGCG: Multiple studies have shown the various benefits of green tea and its polyphenols against cancer. Till recently it wasn't clear how green tea acted against cancer but a recent breast cancer study led by Katherine D. Crew, an assistant professor of medicine and epidemiology at Columbia University Medical Center in New York has shown that chemicals in green tea called polyphenols appear to inhibit two proteins that promote tumor cell growth and migration — namely, the vascular endothelial growth factor (VEGF) and the hepatocyte growth factor (HGF).

A team led by James Cardelli of the Louisiana State University Health Sciences Center in Shreveport, La. Cardelli found similar reductions in the same growth factors with Polyphenon E in prostrate cancer. A new study conducted by food scientists at Penn State University shows that green tea's primary compound — epigallocatechin-3-gallate (EGCG) — may kill oral cancer cells and leave healthy cells unscathed. Scientists believe that EGCG may trigger a process in the mitochondria of cancer cells that leads to early cell death. EGCG already is known to induce cell death in five mesothelioma cell lines. “It looks like EGCG causes the formation of reactive oxygen species in cancer cells, which damages the mitochondria, and the mitochondria responds by making more reactive oxygen species,” said Joshua Lambert, associate professor of food science and co-director of Penn State's Center for Plant and Mushroom Foods for Health. As mitochondria damage continues, the cancer cell further lowers its defenses, making it susceptible to early cancer death.

Various mechanisms of EGCG action against cancer

Studies show tannins and antioxidants in green tea may help slow or prevent the spread of mesothelioma cancer cells. Dry green tea leaves are about 40% polyphenols by weight, and the most potent of these is EGCG. A team of scientists at Purdue University determined: “In the presence of EGCg, the cancer cells literally failed to grow or enlarge after division then presumably because they did not reach the minimum size needed to divide they underwent programmed cell death, or apoptosis.” EGCG, an antioxidant, is considered many times more potent than the Vitamin E or Vitamin C antioxidant properties. In a 1997 study, researchers from the University of Kansas determined that EGCG is twice as powerful as resveratrol, which itself is known to kill cancer cells. In a double-blind, placebo-controlled study, 60 men took 200 mg of green tea catechin or a placebo three times daily for 1 year (62). These men had high-grade prostatic intraepithelial neoplasia, which is thought to be a precursor of prostate cancer. After 1 year, fewer prostate cancers were detected in the green tea catechin group (1 cancer in 30 men) compared with the placebo group (9 cancers in 30 men) (62). Two other clinical trials, both uncontrolled studies, investigated the use of green tea extracts to reduce prostate-specific antigen levels in men with prostate cancer and found no evidence of such a reduction. Reported in the journal Metabolomics, the study explores the effect of epigallocatechin gallate or "EGCG," an active biological agent of green tea. It shows that EGCG changes the metabolism of pancreatic cancer cells by suppressing the expression of lactate dehydrogenase A or LDHA, a critical enzyme in cancer metabolism. one published in 2012 suggested that drinking green tea may lower risk of digestive system cancers in women while another found EGCG delivered intravenously directly to tumors made two-thirds of them shrink or disappear within one month!

23. GRAPE SEED EXTRACTGrape seed extract is an industrial derivative of grape seeds, extremely rich in antioxidants and oligomeric proanthocyanidin complexes. Many studies have reported benefits of grape seed extract against cancer. Researchers at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, tested the impact of grape seed extract in colorectal cancer cell lines at several stages of the disease. They noted an increase in a number of the anticancer mechanisms found within grape seed extract with increasing cancer stages. Chemotherapy has diminishing effectiveness with advanced stages of cancer. 

Unlike chemotherapy which traditionally targets only a specific mutation grape seed extract is able to target multiple mutations. The more mutations found in a case of cancer, the more effective grape seed extract can be in treating the cancerous cells! It is frightening to learn that colorectal cancer cell can exhibit upward of 11,000 genetic mutations. Man made drugs have not been able to go anywhere close to targeting all such mutations making the cancers resistant quite quickly. But nature has provided equally brilliant tools. Research has shown that higher the stage of cancer lesser the amount of grape seed extract needed to inhibit the cancer cells. Actually, the power of grape seed extract seems quite remarkable in this research, which was published in the journal Cancer Letters. Molly Derry, a doctoral candidate in the lab of Rajesh Agarwal, PhD, and investigator at the CU Cancer Center and her team saw that while doses of chemotherapy only increase with more severe cancer cases, such as a stage IV instead of stage II, the amount of grape seed extract required actually decreased. Derry explained:“It required less than half the concentration of GSE to suppress cell growth and kill 50 percent of stage IV cells than it did to achieve similar results in the stage II cells.We’ve known for quite a while that the bioactive compounds in grape seed extract selectively target many types of cancer cells. This study shows that many of the same mutations that allow colorectal cancer cells to metastasize and survive traditional therapies make them especially sensitive to treatment with GSE.” 
The extract kills cancer cells by a process of oxidative stress. Similar study published earlier in the journal Carcinogenesis found that in both cell lines and mouse models, grape seed extract killed head and neck squamous cell carcinoma cells, without harming nearby healthy cells. In that published paper, the authors noted that grape seed extract created an environment unfavorable to cancer cell growth. A study published later, in January 2013, in the journal Nutrition and Cancer, found that grape seed extract was also effective in treating prostate cancers, while a January 2014 published study showed grape seed extract to be effective against certain types of lung cancer. The Australian study found that grape seed extract led to a 55 percent decrease in chemotherapy-induced inflammation and a 26 percent increase in chemotherapy’s ability to kill cancer cells. Capsules rather than powder are “the preferred way to take grape seed extract because (they are) more tolerable  due to (powder’s) astringent taste and unappealing brownish red color,” says Dr. Amy Cheah, a medical science researcher at the school of agriculture, food and wine at Australia’s University of Adelaide, who led the cancer study. In another study reported in medical journal Plos One, demonstrates for the first time that grape seed extract is a wonder supplement in the fight against cancer, aiding chemotherapy’s effectiveness in killing colorectal cancer cells. What’s more, it also reduces chemotherapy’s painful side effects. In study on prostrate cancer on xenograft mice it was found that GSE exerts antiproliferative and antiangiogenic effects and interferes with IGF-1 signaling in DU145 xenografts thereby limiting the cancers progression to more advanced stage. In breast cancer studies antiangiogenic effects of GSE were observed in MDA-MB-231 human breast cancer cells and in U251 human glioma cells. In the study conducted by Mantena et al. (54), the metastatic potential of 4T1 breast cancer cells was inhibited by grape seed proanthocyanidins. Apart from the anticancer and chemopreventive efficacy of GSE against skin, colorectal, prostate, and breast cancers discussed above, anticancer efficacy of this extract has also been observed against human lung cancer A427, A549, and H1299 cells, human gastric adenocarcinoma CRL-1739 cells, oral squamous cell carcinoma CAL27 and SCC25 cells, Jurkat, U937, and HL-60. the other parts of the grape such as the skin, the whole grape by itself, grape-derived raisins, and phytochemicals present within the grapes have also demonstrated potential anticancer efficacy in various preclinical and clinical studies so one can take capsules that not have GSE but also whole grape.

24. ELLAGIC ACID, BERRIES AND POMEGRANATE: Ellagic acid is a phytochemical (polyphenol) that our body produces in the large intestines and is also found in many foods. This special phytochemical has been found to be helpful to those suffering from multiple cancers, including cervical, breast, and prostate cancers. Pomegranate and Berries are good sources of ellagic acid. A study coming from the Hollings Cancer Institute at the University of South Carolina found that in over 500 women studied, all of whom had cervical cancer, almost 85% of participants experienced what is called G-arrest of cancerous cells within 48-72 hours by increasing their ellagic acid consumption. 
Further studies confirmed these results, but now cancer cell apoptosis (cancer suicide) has been confirmed for breast cancer, pancreas cancer, skin, colon, and esophageal cancers as well. The ellagic acid works primarily by stopping mitosis cancer cell division. Further studies are suggesting that ellagic acid inhibits mutagenesis and carcinogenesis by forming adducts with DNA, thus masking binding sites to be occupied by a mutagen or carcinogenic substance. Animal studies on the effect of blueberries and black raspberries on estrogen-positive breast tumors have shown good potential as well. AICR grantee Harini Aiyer, PhD, Postdoctoral Research Fellow at Lombardi Cancer Center, Georgetown University School of Medicine, found that a six-month diet of black raspberries reduced breast tumor volume in rats by 70 percent! A six-month diet of blueberries reduced tumor volume by 60 percent! In cell culture studies, 
Pomegranate Extract
Pomegranate extract (particularly the punicaligans and ellagic acid polyphenols) have been shown to block both tumor growth and metastasis through multiple mechanisms.
 Dr. Aiyer also found that adding ellagic acid to estrogen-positive cells treated with tamoxifen made them less likely to become resistant to the effects of the drug. "If estrogen acts as fuel for some breast cancers, we may be able to use ellagic acid, which acts like an anti-estrogen, to cut off the fuel supply," says Dr. Aiyer. Gary Stoner, PhD, professor at the Medical College of Wisconsin, has been studying the potential of berries for cancer prevention for more than two decades. In his studies, Dr. Stoner found that a diet of freeze-dried black raspberries or strawberries can inhibit esophageal cancer in rats 30-70 percent and colon cancer up to 80 percent! In these studies, the berries were freeze-dried then ground into a powder.
From recent early phase clinical studies, Dr. Stoner and his colleagues found that black raspberry and strawberry powders are safe and well tolerated. 

25. TRAIL: Metastasis is the spread of cancer cells from one tumor to other organs of the body, such as the lungs, the liver, the spleen and the kidneys. While surgery and radiation treat primary tumors, it remains difficult to detect and reach metastatic cancer cells – which makes the treatment of spreading cancer more treacherous and problematic. Metastasis is the cause related to 90% of cancer deaths! Therefore it is really exciting to come across a therapy that specifically targets cancer cells spreading in the bloodstream. 
Handsome and brilliant biomedical engineering professor Michael King of Cornell University discovered a protein and a method to stick it to our white blood cells - leukocytes. This combination then turns into hunters for cancer cells in the bloodstream and destroy the cancer cells upon contact. King and his colleagues injected at first human blood samples and later mice with two proteins E-Selectin (an adhesive) and TRAIL (Tumor Necrosis Factor Related Apoptosis Inducing Ligand). King’s laboratory created nano-sized liposomes with a protein called TRAIL The liposomes are about one-one hundredth the size of the white blood cells. The TRAIL protein joined with E-Selectin protein stick to leukocytes. in the bloodstream. When a cancer cell comes in contact with the TRAIL leukocyte which becomes unavoidable in the chaotic blood flow the cancer cell kills itself. "The mechanism is surprising and unexpected in that this repurposing of white blood cells in flowing blood is more effective than directly targeting the cancer cells with liposomes or soluble protei" say the authors.
When they added the Proteins to flowing blood in the laboratory the success rate in killing cells was 100%! 
TRAIL cells
A robust amount of the therapeutic, cancer-killing TRAIL protein, shown in green, bound to the surface of natural killer cells - making them "super natural killer cells" - collected from the mouse lymph node 24 hours after treatment. source Cornell University 
In a study published in Journal Biomaterials on November 2, 2015 Kings super natural killer cells seeked out and destroyed lymph node tumors. “We want to see lymph node metastasis become a thing of the past,” said King the author of the paper, “Super Natural Killer Cells That Target Metastases in the Tumor Draining Lymph Nodes.” For tumor cells, the lymph nodes are a staging area and play a key role in advancing metastasis throughout the body. In the study, the biomedical engineers killed the cancerous tumor cells within days, by injecting liposomes armed with TRAIL (Tumor necrosis factor Related Apoptosis-Inducing Ligand) that attach to “natural killer” cells (a type of white blood cell) residing in the lymph nodes.These natural killer cells became the “super natural killer cells” that find the cancerous cells and induce apoptosis, where the cancer cells self-destruct and disintegrate, preventing the lymphatic spread of cancer any further, said King. explaining further, “In our research, we use nanoparticles – the liposomes we have created with TRAIL protein – and attach them to natural killer cells, to create what we call ‘super natural killer cells’ and then these completely eliminate lymph node metastases in mice,”  n cancer progression, there are four stages. At stage I, the tumor is small and has yet to progress to the lymph nodes. In stages II and III, the tumors have grown and likely will have spread to the lymph nodes. At the stage IV, the cancer has advanced from the lymph nodes to organs and other parts of the body. I“So, now we have technology to eliminate bloodstream metastasis – our previous work – and also lymph node metastases,” King said. In their upcoming and latest publication on February 10th 2016 on cover page of Journal of Controlled Release King and his team demonstrate success of their technology in mouse models. The therapy is remarkably effective in vivo and shows several advantages, such as no toxicity and getting good results in very low dosages,” said King,“It was our wildest dream to completely prevent the spread of prostate cancer. And that’s what happened in this system.” In this latest study prostate cancer cells were implanted into the prostate of male mice to let the tumors grow. The researchers found that secondary tumors were prevented by the treatment and that the primary tumor shrunk in size. Further, the King group found that a single dose of the therapy – even delivered very late in the course of the disease – can substantially reduce the number of tumor cells. King said: “This suggests that it may never be too late to help.” Further animal studies will hopefully lead to human clinical trials so that millions of cancer patients can benefit from this technology. 

26. ANETHOLE: Within the essential oils of anise, camphor, and fennel is a substance called Anethole. It is used as a flavoring and fragrance agent and is one of the main ingredients in absinthe. Interestingly it is 13 times sweeter than sugar so can be used instead of sugar. It is a precursor to the drug PMA colloquially known as ecstasy. 
Star Anise

Fennel Seeds

In a study conducted by department of Nutrition, University of Texas at Austin  Anethole suppressed cell survival and induced apoptosis in human breast cancer cells independent of estrogen receptor status. They concluded: anethole in an ER independent manner suppresses cell survival and induces apoptotic events in MCF-7 and MDA-MB-231 at an optimal concentration of 1 × 10(-3)M. In search of alternative compounds for therapeutic development, this study has demonstrated that anethole may be viable as an anti-cancer agent through the modulation of apoptosis, cell survival and proliferation in breast cancer cells. A study by M.D. ANderson Cancer Center they discovered that anethole inhibits TNF-induced cellular responses, which may explain its role in suppression of inflammation and carcinogenesis. In another study by University of Texas at Austin concluded that anethole is a potential anti-tumor agent, and that co-treatment of tamoxifen and anethole is a potential approach to sensitize human breast MCF-7 cells to tamoxifen treatments. According to an article in the journal Nature, anethole has the effect of blocking "early and late cellular responses transduced by tumor necrosis factor", which means it may help stop the spread of cancer. In a clinical study published by Samarjit Jana of West Bengal State University it was found that when Cyclophosphamide (100 mg kg−1) was injected into anethole treated or untreated tumor bearing mice for 3 consecutive days results demonstrated that anethole and cyclophosphamide, singly as well as in combination, reduced tumor load to a significant extent. 
Graphical abstract: Antitumor potential of anethole singly and in combination with cyclophosphamide in murine Sarcoma-180 transplantable tumor model
Cyclophosphamide+anethole exhibited significantly more tumoricidal activity than anethole alone. Induction of apoptosis was found in anethole-treated groups. Importantly use of anethole was instrumental in reducing the side-effects. The study indicates that anethole pre-treatment protected the bone marrow, liver and urinary bladder from the adverse toxicity of cyclophosphamide without interfering with its anticancer effect. The following are the benefits from anethole derivatives: Anethole ditholethione significantly reduce lung cancer progression; Another constituent, anethole trithione inhibits mammary cancer multiplicity and colon carcinogenesis; 

27. SANGUINARINE: An alkaloid found in Bloodroot roots has shown anti cancer activity against many cancers in multiple peer reviewed studies. In study conducted by University of Wisconsin Medical Science Center it was found that Sanguinarine causes cell cycle blockade and apoptosis of human prostate carcinoma cells via modulation of cyclin kinase inhibitor-cyclin-cyclin-dependent kinase machinery. A highlight of this study was the fact that sanguinarine induced growth inhibitory and antiproliferative effects in human prostate carcinoma cells irrespective of their androgen status. To the researchers knowledge, this is the first study showing the involvement of cyclin kinase inhibitor-cyclin-cyclin-dependent kinase machinery during cell cycle arrest and apoptosis of prostate cancer cells by sanguinarine. These results suggest that sanguinarine may be developed as an agent for the management of prostate cancer. In another study published by Case Western University differential antiproliferative and apoptotic response of sanguinarine for cancer cells versus normal cells was found. Their researchers too concluded that sanguinarine could be developed as an anticancer drug. In a recent study Christina Kalogris of the University of Camorino and colleagues concluded that sanguinarine suppresses basal-like breast cancer growth through dihydrofolate reductase inhibition. These results provide evidence that sanguinarine is a promising anticancer drug for the treatment of BLBC. 
In study published in Toxicology Letters it was reported that Sanguinarine induces apoptosis in human colorectal cancer HCT-116 cells through ROS-mediated Egr-1 activation and mitochondrial dysfunction. The highlights of the study results were: Sanguinarine induces apoptosis. • ROS is involved in sanguinarine-induced apoptosis.• Sanguinarine induces mitochondrial dysfunction and activates caspase cascade.• ROS-dependent Egr-1 activation is involved in sanguinarine-induced apoptosis. In another study published in PLoS ONE in 2013 it was reported that Apoptosis Induction of Human Bladder Cancer Cells by Sanguinarine through Reactive Oxygen Species-Mediated Up-Regulation of Early Growth Response Gene-1. The exciting conclusion was that their data provides evidence that sanguinarine is a potent anticancer agent, which inhibits the growth of bladder cancer cells and induces their apoptosis through the generation of free radicals. In a study published in Oncology Reports it was concluded by researchers that Sanguinarine inhibits growth of human cervical cancer cells through the induction of apoptosis. Their further stated that their findings indicate that sanguinarine as an effective anticancer drug candidate inhibits the growth of cervical cancer cells through the induction of apoptosis. In a study led by Ana Burgeiro they found rapid human melanoma cell death induced by sanguinarine through oxidative stress. She concluded that our data indicates that
sanguinarine is a very rapid inducer of human melanoma caspase-dependent cell death that is
mediated by ROS generation. Dr. Veronique Desaulniers has some interesting things to say on bloodroot in an article titled 'Could this be breast cancer's achilles heel' She says there is a protein that cancer cells produce called “Survivin”. This protein prevents them from dying by inhibiting certain chemical pathways that all healthy cells eventually go throughSurvivin is highly expressed in cancer cells and is associated with chemotherapy resistance, increased tumor recurrence and shorter patient survival. She shared that when she was on her personal healing journey, she used Blood Root internally and applied it externally on the unhealthy tissue in her breast. The phytochemical found in blood root: Sanguinarine is known to down regulate survivin and induce apoptosis or cancer cell death, without harming healthy cells.

28. METRONOMIC CHEMO: UFT + CTX + DC101: The only reason this option is listed here is because it is shown to be non-toxic or wth very low toxicity. We have no problem with allopethic medicine if it is efficient and it is not toxic to us. In preclinical animal trials reported in low dose UFT (5-fluorouracil) and CTX (cyclophospamide) and DC101 (anti-angiogenesis agent) when administered in a metronomic basis (low drug doses at close regular intervals with no significant breaks) not only proved to be non-toxic but also showed significant efficacy against some metastastic breast and liver cancers. In eight of these clinical trials, which included almost 500 patients in total, metronomic chemotherapy alone or in combination with letrozole trastuzumab or bevacizumab, was shown to be an effective approach. Furthermore it was associated with minimal toxic effects for either primary systemic or palliative treatment of advanced, metastatic and/or resistant breast cancer patients. The average response rates—complete response (CR) plus partial response (PR)—and overall clinical benefit (CR + PR + stable disease [SD] >6 months) of metronomic chemotherapy reported in these studies were 39% (range 12–88%) and 57% (range 24–93%), respectively. Positive results were also reported with various metronomic chemotherapy regimens for patients with recurrent ovarian cancer, hormone-resistant prostate cancer advanced multiple myeloma, recurrent non-Hodgkin's lymphoma, recurrent malignant glioma and glioblastoma, metastatic or locally advanced neuroendocrine carcinoma[35] and advanced cancer of various tumor types. These clinical studies, which included more than 500 patients in total, showed an average response rate to metronomic chemotherapy and overall clinical benefit of 33% (range 13–69%) and 61% (range 30–93%), respectively. Relatively disappointing results obtained with metronomic chemotherapy were exclusively reported in malignancies that are poorly responsive to conventional chemotherapy and with a dismal prognosis. A recent phase II trial has reported very promising results in metastatic renal-cell carcinoma patients using a combination of metronomic capecitabine, sorafenib and gemcitabine, with a response rate of 50% and a clinical benefit of 92.5%. Overall, metronomic chemotherapy is associated with minimal toxicity and can provide significant clinical benefit and improve the quality of life of patients with advanced and/or relapsed cancer. 
Emerging evidence suggests that some chemotherapeutic drugs commonly used in metronomic protocols may act not only by inhibiting tumor angiogenesis but also by restoring anticancer immune response. It selectively inhibits immunosuppressants. There is no trial proving universal efficacy of metronomic chemotherapy. Each individual type of cancer would require a tailor made combination to be given via metronomic methods to discover the most effective combination. 
SYNERGY: METRONOMIC CHEMO + NATURAL ANGIOGENESIS INHIBITORS: Another approach that I am suggesting for further investigation is combination of metronomic chemotherapy whose main action is angiogenesis inhibition with natural angiogenesis inhibitors. Some of the natural products that have shown such prowess are Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (curcumin), Scutellaria baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green tea), Ginkgo biloba, quercetin, Poria cocos, Zingiber officinalis (ginger), Panax ginseng, Rabdosia rubescens hora (Rabdosia), and Chinese destagnation herbs. A recent  It seems majority of people carry around microscopic cancer cell clusters in their bodies, but not everyone actually develops cancer. This is because as long as your body has the ability to balance angiogenesis properly, it will prevent blood vessels from forming to feed these microscopic tumors. Trouble will only arise if, and when, the cancer cells manage to get their own blood supply, at which point they can transform from harmless to deadly. esveratrol from red grapes, for example, have been shown to inhibit abnormal angiogenesis by 60 percent. foods equaling or exceeding the potency of drugs include parsley, garlic, and red grapes. Grape seed extract is well tolerated and has shown VGEF inhibition. 

29. COPPER CHELATION: A recent 2014 study in BMC Cancer journal demonstrated that copper chelation using agent TPEN (5um) led to selective elimination of colon cancer cells by way of angiogensis cascade. Copper chelation using TM has demonstrated efficacy in preclinical and animal models as an alternative and novel anti-angiogenic agent. Phase I and II clinical trials conducted in solid tumors using TM have demonstrated efficacy with favorable toxicity profile. Copper chelation using TM (Tetrathiomolybdate) has demonstrated efficacy in preclinical and animal models as an alternative and novel anti-angiogenic agent. Phase I and II clinical trials conducted in solid tumors using TM have demonstrated efficacy with favorable toxicity profile. Lowering copper levels could prove a useful strategy for treating cancers possessing a common mutation in the BRAF oncogene, reports a US study in Nature. An anti-copper drug compound that disables the ability of bone marrow cells from setting up a "home" in organs to receive and nurture migrating cancer tumor cells has shown surprising benefit in one of the most difficult-to-treat forms of cancer — high-risk triple-negative breast cancer. The median survival for metastatic triple-negative breast cancer patients is historically nine months. 
However, results of a new phase II clinical trial conducted by researchers at Weill Cornell Medical College and reported in the Annals of Oncology shows if patients at high-risk of relapse with no current visible breast cancer are copper depleted, it results in a prolonged period of time with no cancer recurrence. In fact, only two of 11 study participants with a history of advanced triple-negative breast cancer relapsed within 10 months after using the anti-copper drug, tetrathiomolybdate (TM). "These study findings are very promising and potentially a very exciting advance in our efforts to help women who are at the highest risk of recurrence," says the study's senior investigator, Dr. Linda Vahdat, director of the Breast Cancer Research Program, chief of the Solid Tumor Service and professor of medicine at Weill Cornell Medical College.Dr. Vahdat says four of the study participants with a history of metastatic triple-negative breast cancer have had long-term benefit remaining disease free for between three and five and a half years."The anti-copper compound appears to be keeping tumors that want to spread in a dormant state," reports Dr. Vahdat, "We believe one of the important ways it works is by affecting the tumor microenvironment, specifically the bone marrow-derived cells that are critical for metastasis progression." In addition, study participants with other forms of high-risk for relapse breast cancers — either stage 3 or stage 4 — without evidence of disease after treatment have also fared well. The progression-free survival rate among these 29 patients in the study has been 85 percent, to date. Dr. Vahdat expects to launch a phase III randomized clinical trial in the near future. Copper is essential to the metastatic process. It is a key component of enzymes that help turn on angiogenesis in the tumor microenvironment, and it also appears to play a role in directing cancer cell migration and invasion, according to researchers.  In the study, researchers found that 75 percent of patients achieved the copper depletion target using TM after one month of therapy, and that copper depletion was most efficient (91 percent) in patients with triple-negative tumors, compared to other tumor types (41 percent). In copper-depleted patients only, there was a significant reduction in EPCs, and the 10-month relapse-free survival was 85 percent. In addition, TM was found to be safe and well-tolerated in patients. Copper-chelating agents appear to be useful in cancer treatment in ways unrelated to angiogenesis; they can also be cytotoxic to cancer cells. D-penicillamine (D-pen), another copper-chelating agent, can generate intracellular reactive oxygen species (ROS) and be cytotoxic to human leukemia and breast cancer cells. A 2010 study on head and neck squamous cell carcinoma (HNSCC) showed that tetrathiomolybdate can act long term as a suppressor of vascularity and inhibit the growth of metastasis of HNSCC. Tetrathiomolybdate treatment drastically suppressed the development of lung metastases. Copper depletion therapy is shown to be safe and nontoxic. The main side effect is anemia, which can be easily monitored.

30. VITAMIN D: .It's virtually impossible to discuss cancer prevention today without discussing vitamin D, as the scientific evidence of its anti-cancerous benefits is truly impressive. Intake of vitamin D3 and calcium could potentially prevent 58,000 new cases of breast cancer and 49,000 new cases of colorectal cancer annually in the United States and Canada, according to a complex computer prediction model. This model also predicted that 75 percent of deaths from these cancers could be prevented with adequate intake of vitamin D3 and calcium. Theories linking vitamin D to certain cancers have been tested and confirmed in more than 200 epidemiological studies and understanding of its physiological basis stems from more than 2,500 laboratory studies, according to epidemiologist Cedric Garland, professor of family and preventive medicine at the UC San Diego School of Medicine. According to Garland, in nearly all forms of breast cancer, vitamin D affects the structure of your epithelial cells. These cells are held together by a glue-like substance called E-cadherin, which provides structure to the cell. E-cadherin is made up of mostly vitamin D and calcium.If you don't have adequate vitamin D, that structure comes apart and those cells do what they are programmed to do in order to survive — they go forth and multiply. If this growth process (cell proliferation) gets out of control, you may end up with cancer.If you have breast cancer in progress, the addition of vitamin D can help stop cancer cells in their tracks by replenishing E-cadherin. Once cancer growth is slowed, your immune system can begin to get ahead of the cancer cells, because it doesn't have to deal with gazillions of them. It's just disposing of the "leftovers." The theory above is Dr. Garland's DINOMIT theory and has been substantiated by subsequent studies by other researchers.
The DINOMIT Model of Age-Related Cancer stresses a person's serum 25(OH)D and calcium levels, while downplaying the importance of family history.
Disjunction - Inadequate serum 25(OH)D levels results in the intracelluar junction breaking down between cells resulting in a loss of intracellular communication. The cells pull apart and have a potential of being autonomous. 
Initiation - The newly devolved cells become more rapidly reproducing. Either the process of the reproduction of these cells at an accelerated rate results in uncorrected errors that occur during DNA replication; Or, a environmental trigger is provided by a carcinogen that results in genetic mutation variation. 
Natural Selection - The fastest-reproducing cancer cells soon dominate the entire tissue compartment by the process of Darwinian evolution. 
Overgrowth - Cancers cells multiply enough for a tumor to be clinically detectable to the point where it takes over the entire tissue compartment. 
Metastasis - Cancer cells begin to break through the stroma, or the connective tissue, to the rest of the organ and ultimately to the entire body when cancer cells start to migrate to other tissues, such as the brain, lungs, and liver through the lymphatic system or blood circulation. These aggressive cells enzymatically dissolve the membrane of connective tissue presumably in order to obtain needed amino acids. 
Involution - Malignant cells may enter a stage of slowed or arrested growth which normally occurs during the summer months when blood levels of vitamin D are naturally at their highest levels, or after optimum blood levels of have been restored.
Transition - The cancer becomes a chronic condition if vitamin D and calcium are repleted to adequate levels. But, if vitamin D and calcium deficiency persist the cancer becomes an acute condition, the malignancy grows further until ultimately causing death. Restoring vitamin D and calcium to adequate levels is capable of reversing the degenerative process throughout the seven phase life cycle of cancerous cells and their progeny as long as the malignant cells still have an intact vitamin D receptor (VDR).
Restoring vitamin D and calcium to adequate levels reconnects the devolved cells or reestablishes intercellular tight junctions and inhibits cell mitosis or reproduction.
In a separate process, adequate levels of vitamin D strengthens your innate immune system with natural killer cells that will surround individual malignant cells and kill them. 50 ng/ml is the minimum serum level one needs to maintain. The best way to get vitamin D level is by early morning (ideally before 9.30 am) sunlight. 30 minutes of sunlight all over or atleast most parts of your skin is useful to achieve the needed levels. 
Recent findings by St. George’s Hospital Medical School in London found that women with low breast tissue levels of vitamin D actually increase their risk of breast cancer by 354% What’s more, in a world first, the same researchers discovered that breast tissue actually produces a cancer-fighting compound called calcitriol. This compound is known to completely destroy breast cancer tumors. But for the body to make calcitriol, the breast tissue needs vitamin D. And the best way to get vitamin D is from the sun.This is why researchers recommend women sunbathe everyday with the breasts exposed, to enhance local vitamin D production and produce calcitriol.

31. KETOGENIC (FATTY) DIET + OXYGEN: Ketogenic diet and hyperbaric oxygen has shown remarkable results in a study published in PLoS Journal. Angela Poff from University of South Florida led this study. Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD) is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO2T) saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease. KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. While HBO2T alone did not influence cancer progression, combining the KD with HBO2T elicited a significant decrease in blood glucose, tumor growth rate, and an astonishing 77.9% increase in mean survival time compared to controls. KD and HBO2T produce significant anti-cancer effects when combined in a natural model of systemic metastatic cancer. Evidence suggests that these therapies should be further investigated as potential non-toxic treatments or adjuvant therapies to standard care for patients with systemic metastatic disease.  
Starving Cancer Cells of Sugar

Some earlier case studies of ketogenic diet: in 1995 in which two girls with inoperable astrocytomas were placed on a ketogenic diet  Within 7 days of initiating the ketogenic diet, blood glucose levels declined to low-normal levels and blood ketones were elevated twenty to thirty fold. Results of PET scans indicated a 21.8% average decrease in glucose uptake at the tumor site in both subjects. One patient exhibited significant clinical improvements in mood and new skill development during the study. She continued the ketogenic diet for an additional twelve months, remaining free of disease progression. In another experiment on brain cancer KetoCal administered in restricted amounts significantly decreased the intracerebral growth of the CT-2A and U87-MG tumors by about 65% and 35%, respectively, and significantly enhanced health and survival relative to that of the control groups receiving the standard low fat/high carbohydrate diet This preclinical study indicates that restricted KetoCal is a safe and effective diet therapy and should be considered as an alternative therapeutic option for malignant brain cancer. The best thing about this development is that this would turn out to be amongst the most pleasant therapies discovered against cancer. Who wouldn't like to eat a fatty diet and inhale lots of oxygen for slowing down their cancer?

32. LYMPHOCYTE EXPANSION MOLECULE: In a discovery that is being hailed as a game changer in cancer therapeutics researchers at Imperial college discovered A protein which ‘turbo-charges’ the immune system so that it can fight off any cancer or virus has been discovered by scientists. Unfortunately there may not be an immediate benefit to cancer patients from this discovery but Scientists at Imperial College London, who led the study, are now developing a gene therapy based on the protein and hope to begin human trials in three years. “This is exciting because we have found a completely different way to use the immune system to fight cancer,” said Professor Philip Ashton-Rickardt, from the Section of Immunobiology in the Department of Medicine at Imperial, who led the study. “This is a completely unknown protein. Nobody had ever seen it before or was even aware that it existed. It looks and acts like no other protein.” The protein – named lymphocyte expansion molecule, or LEM, promotes the spread of cancer killing ‘T cells’ by generating large amounts of energy. Normally when the immune system detects cancer it goes into overdrive trying to fight the disease, flooding the body with T cells. But it quickly runs out of steam. However the new protein causes a massive energy boost which makes T cells in such great numbers that the cancer cannot fight them off.
LEM causes a flood of T-Cells that overwhelm Cancer Cells

It also causes a boost of immune memory cells which are able to recognise tumours and viruses they have encountered previously so there is less chance that they will return.
The team made the discovery while screening mice with genetic mutations. They found one type produced ten times the number of cancer-fighting T cells, suppressing infections and becoming resistant to cancer.Researchers found that the mice with enhanced immunity produced high levels of the unknown protein which is also found in humans.They are hoping to produce a gene therapy whereby T cells of cancer patients could be enhanced with the protein and then injected back into the body. It could end the need for harsh chemotherapies as the body itself would be fighting the disease, rather than toxic drugs. Charities said the protein showed 'great promise' and were eager to see if it could be translated into humans. 

33. IBRUTINIB: This incredible breakhrough drug although quite expensive has shown astounding results in some blood cancers without the brutal side effects of chemotherapy. This revolutionary drug ‘switches off’ cancer and may soon be offered to patients with some forms of the disease. Wondeful news for cancer patients is that it is just like taking any vitamin pill - one tablet a day is all it needs to show these unbeleivable results. It is a new class of targeted medications, known as a Bruton’s tyrosine kinase inhibitor. It works by targeting and switching off a protein in the cancer cells. This drug is targeted at the B-cells, the side effects are minor. Patients don’t have to go into hospital to have it administered! It costs 74,000 pounds a year in UK. It is one of only a handful of new medicines to be made available via the Cancer Drugs Fund after two trials in 28 British hospitals showed it to be extremely effective in treating both mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia (CLL). In Australia patients will also get access very soon. Earlier results of a trial on 391 patients showed the drug Ibrutinib gave patients fighting a type of slow growing blood cancer called Chronic lymphocytic leukaemia (CLL) a 90 per cent chance of survival. It was found that the drug is less invasive than traditional forms of radiation, and is an alternative for patients whose cancer cells have built up a resistance to chemotherapy. Results from the trial also showed that four out of every 10 patients entered remission within a year, compared to four in 100 on a traditional course of radiation. The trial has Dr Con Tam of Melbourne's Peter MacCallum Cancer Centre confident that Ibrutinib will eventually replace chemotherapy as the main treatment for leukaemia patients. He told AAP: 'We might not need chemotherapy at all. It is also being fast tracked in USA for approvals. It is also being tested for lung cancer. In a study it was also shown to inhibit breast cancer. It is branded as IMBRUVICA is jointly developed and commercialized by Pharmacyclics and Janssen Biotech, Inc. Synergistic deployment with PD-L1 antibody also has shown remarkable success. The combination of an anti-PD-L1 antibody and ibrutinib resulted in suppression of tumor growth and extension of survival in a mouse model of lymphoma. The study found while some of the mice responded to anti-PD-L1 treatment alone, the response eventually diminished over time. When ibrutinib was added to anti-PD-L1 treatment, half of the mice were cured and the other half experienced delays of tumor growth and prolonged survival.
The researchers also chose two solid tumor models to investigate the novel combination – triple negative breast cancer and colon cancer, which do not express BTK (Bruton's tyrosine kinase) and have low levels of the PD-L1 protein. When ibrutinib and the PD-L1 antibody were given as single agents neither had any effect on tumor growth. However, the combination reduced the size of the primary tumors, improved survival and resulted in fewer metastases in both breast and colon cancer. Specifically, in the case of the colon cancer tumor model, approximately 30% of the mice were cured.

Most importantly, the researchers tested whether the mice cured from colon cancer had developed long-term immune memory, specific memory T cells, from the novel combination. These mice were re-exposed to colon cancer cells 90 days post cure and after seven days of tumor growth, all the mice cleared the tumor by day 17 without any additional dosing of the ibrutinib and PD-L1 combination.
CLL Leukemia cell. 24-month overall survival rate for patients taking ibrutinib was 97.8%
 Programmed death-ligand (PD-L1) is a protein that may suppress the ability of the immune system to fight diseases. In certain cancers, PD-L1 may play a role in inhibiting the ability of T cells (necessary to help the body fight disease) to function properly, which results in the proliferation of tumors in the human body. Anti-PD-L1 antibody therapies have been shown to block the negative effect that PD-L1 can have on T cells, allowing certain cancers to be successfully treated. Recent pre-clinical studies have also demonstrated that ibrutinib, which has been shown to be effective in treating B-cell mediated cancers, can also inhibit interleukin-2-inducible T-cell kinase (ITK), an enzyme important in regulating T-cell effector function. This activity may be relevant to the mechanism by which ibrutinib enhances the efficacy of check point inhibitors. Over 5,100 patients have been treated in clinical trials of IMBRUVICA conducted in 35 countries by more than 800 investigators. Currently, 13 Phase III trials have been initiated with IMBRUVICA and 58 trials are registered on www.clinicaltrials.govIMBRUVICA was one of the first medicines to receive U.S. FDA approval via the new Breakthrough Therapy Designation pathway, and is the only product to have received three Breakthrough Therapy Designations. It is no doubt one of the most exciting developments for cancer patients.

34. AVEMAR: Fermented wheat germ (Saccharomyces cerevisiae) made by a standardized, patented process, and named Avemar. It seems to have multiple actions against cancer. In a study done by Saiko of the Medical University of Vienna he reports that Avemar (MSC) is a nontoxic fermented wheat germ extract demonstrated to significantly improve the survival rate in patients suffering from various malignancies. We investigated its effects in human HL-60 promyelocytic leukemia cells. After 24, 48, and 72 h of incubation, Avemar inhibited the growth of HL-60 cells with IC50 values of 400, 190, and 160 microg/ml, respectively. Incubation with MSC caused dose-dependent induction of apoptosis in up to 85% of tumor cells. In addition, Avemar attenuated the progression from G2-M to G0-G1 phase of the cell cycle and was also found to significantly reduce the in situ activity of ribonucleotide reductase, the key enzyme of de novo DNA synthesis. We conclude that Avemar exerts a number of beneficial effects which could support conventional chemotherapy of human malignancies. The incredible finding shows  apoptosis in 85% of the cancer cells! Some other studies show that it:
  • Reduces cancer recurrence – one study of 170 colorectal cancer patients showed a 67 percent reduction in metastasis and 62 percent reduction in deaths in the group who used Avemar compared to the control group that didn’t.
  • Cuts off cancer cell’s energy supply by selectively inhibiting glucose metabolism in cancer cells (the higher the glucose; the greater chance of spreading)
  • Speeds cancer  cell death by inhibiting the production of PARP, which enables DNA replication of cancer cells
  • Exposes “undercover” cancer cells by helping the immune system identify cancer cells for attack by suppressing their ability to generate a surface molecule called MHC-1, which tells natural killer cells not to attack. 
  • Actions of Avemar:


In more than 100 studies it has also shown to :
  • Up regulate Th1(cellular) immune function, while inhibiting Th2 (humoral)immune function.
  • Reduce inflammation and symptoms of Rheumatoid arthritis, systemic lupus erythematosus (SLE) and other autoimmune diseases associated with the predominance of Th2 over Th1 immune response.
  • Restore the bone marrow's ability to produce red blood cells.
  • Provide immuno-regulating capabilities. In autoimmune diseases it is immunosuppressive and in malignancies it stimulates the immune system.
  • Can benefit patients with all types of
    cancer - it is not specific
  • Prevent cancer related cachexia
  • Prevent cancer cell proliferation.
  • Inhibit cancer cell motility.
  • Stimulate cancer cell apoptosis [programmed cell death]
  • Enhance the ability of NK cells to identify and kill cancerous and other target cells by down regulating the presentation of MHC-I molecules on infected cells.
  • Stimulate the production of TNF-alpha by macrophages.
  • Enhance the tumour invasive potential of immune system cells by up regulating ICAM-A molecules in micro-vascular endothelial cells.
  • Act as an Autoimmune Treatment
Fermented Wheat Germ Kills All Types of Cancers
 In another study Against the mouse ER+ cell line, MXT, Avemar inhibited growth by 50%, Aromasin by 46.7%, Tamoxifen by 34% and Arimidex by 29.3%. Against the human ER+ cell line, T47T, Avemar inhibited growth by 49%, Tamoxifen 42%, Aromasin 25% and Arimidex 25%. Each agent was enhanced by 5 to 10% when combined with Avemar. Most effective was a combination of Aromasin and Avemar, inhibiting both the mouse and human derived ER+ breast tumors by 60%! Researchers at UCLA have demonstrated that Avemar reduces the flow of glucose into the cancer cells. Cancer cells can evade NK [natural killer] cells by masking their outer membrane with a special substance. Avemar suppresses the release of this masking substance, which allows natural killer cells to better target and kill the cancer cells. Avemar's immune-stimulating ability appears to be so powerful it can be useful in helping to restore even the most severely compromised immune systems.

35. ARTEMISINN + IRON: It is an extract of Sweet Wormwood herb. In a remarkable dscovery by Henry Lai an Narendra Singh of Washngton University a new patented compound was created binding artemisinin with iron. "By itself, artemisinin is about 100 times more selective in killing cancer cells as opposed to normal cells," Lai said. "In this study, the new artemisinin compound was 34,000 times more potent in killing the cancer cells as opposed to their normal cousins. So the tagging process appears to have greatly increased the potency of artemisinin's cancer-killing properties." The compound has been licensed to Chongqing Holley Holdings and Holley Pharmaceuticals, its U.S. subsidiary, to be developed for possible use in humans.
In the study, researchers exposed human leukemia cells and white blood cells to the compound. While the leukemia cells quickly died, the white blood cells remained essentially unharmed.
The trick to the compound's effectiveness, according to Lai, appears to be in taking advantage of how cancer cells function. 
 Because they multiply so rapidly, most cancer cells need more iron than normal cells to replicate DNA. To facilitate that, cancer cells have inlets on their surface, known as transferrin receptors, in greater numbers than other cells. Those receptors allow quick transport into the cell of transferrin, an iron-carrying protein found in blood. n creating the compound, researchers bound artemisinin to transferrin at the molecular level. The combination of the two ingredients appears to fool the cancer cell. 

36. CALCIUM D-GLUCARATE: This ia calcium salt bu can do miraculous benefits for the detox process that liver does for us especially in removing carcinogens from our body and thereby preventing cancers. Jon Barron has a written a fascinating explanation of what exactly calcium d-glucarate can do for us: The main process that liver uses for detoxification is called conjugation - - literally combining toxins with other substances to neutralize them or prepare them for elimination. Amongst other things it combines glucoronic acid with carcinogens such as synthetic estrogens in a process called glucuronidation (the main focus of this newsletter) whereby toxins are literally "washed" from the body. This glucuronidation is one of the main ways the body purges itself of carcinogenic substances. In times past, glucuronidation was sufficient to protect us from cancer. Two things have changed in the last hundred years that contribute significantly to the increase in the incidence of cancer we now see.
  1. We are exposed to far more carcinogens in our food supply, water, and air than ever before. (For example, there are over 2,000 known carcinogens just in the average drinking water in the United States today.)
  2. Thanks to changes in diet and the overuse of antibiotics in medicine and our food supply, the levels of the enzyme called beta-glucuronidase are much much higher in our bodies than ever before.
A book to read

Beta-glucuronidase is an enzyme produced by E. Coli bacteria in the gut. Glucuronidase literally breaks the bond between the toxic compounds the body is trying to eliminate and the glucuronic acid that is responsible for eliminating them. When beta-glucuronidase breaks the bond, the hormone or toxin is once again released into the body instead of being excreted. Elevated glucuronidase activity is associated with an increased risk for various cancers, particularly hormone-dependent cancers like breast, prostate, and colon cancers.
Can we reduce our exposure to beta glucuronidase? Absolutely. Calcium D-Glucarate (a calcium salt found in foods such as apples, grapefruit, broccoli, Brussels sprouts, cabbage, lettuce, and alfalfa) suppresses beta-glucuronidase and restores the glucuronidation detoxification pathway. The beauty of Calcium D-Glucarate is that not only does it neutralize the effects of beta-glucuronidase, but it actually strengthens the bond between glucuronic acid and the cancer-causing toxins that are being flushed from the body. Since the activity of glucuronidase is inhibited when we supplement with D-Glucarate, the body is better able to get rid of the various toxic chemicals and excess hormones that might stimulate tumor formation. Studies in animals have shown that supplementing with D-Glucarate blocked tumor formation in over 70% of the animals tested, and this has been confirmed in studies with human tumor cells. The bottom line is that D-Glucarate lowers the level of glucuronidase, and in so doing allows the body to eliminate harmful carcinogens thereby stopping many tumors, including those of the colon, lungs, liver, breast, skin, and prostate from ever forming. In addition, studies have shown that D-Glucarate can actually shrink those tumors even if they are already well developed. 
Oranges, Apple and Broccoli are sources of calcum d-glucarate

By supplementing the diet with D-Glucarate, we can block glucuronidase activity, and the body can rid itself of carcinogens, thus inhibiting the onset of many forms of cancer, including lung, breast, prostate, and colon. Since the effect of a single low dose can last for hours, manufacturers recommend a daily intake of 400 to 600 mg of D-Glucarate split between two doses, morning and evening. Higher amounts (1,000 to 2,000 mg per day) are typically recommended for individuals with existing cancer. (Note: D-Glucarate is widely available in health food stores and over the internet.). There may be a danger of glucoridation of hormones till the time of supplementation. Of course this redution of hormones occurs at much higher doses. Protection against one particular research toxin (7,12-DMBA) has been noted with acute usage of 9mmol/kg calcium-D-glucarate (4.5mmol 3 hours prior to and another dose 30 minutes prior to DMBA injections) which reduced tumor occurrence from 100% to 30% and studies with more chronic loading have noted benefit with dietary supplementation of 75mmol/kg (of the diet, 5.37mmol/kg bodyweight and 213mg/kg human equivalent). This protective effect extends beyond breast cancer and is able to attenuate skin cancer with either calcium-D-glucarate itself or the main bioactive metabolite (skin cancer is known to be able to be induced by DMBA) and may also extend to DMBA induced oral cancers. Protective effects have also been noted in colon cancer (with potassium hydrogen glucaric acid 140mmol/kg feed but as potassium hydrogen carbonate was inactive the bioactive appears to be glucaric acid) induced by the toxin azoxymethane, which normally induces activity of β-glucuronidase and inhibitors in general have antitumor effects.This study noted that tumor size and multiplicity was reduced to approximately 60% of control! There is tumor inhibition shown for breast, prostate, lung, and colon cancer, and the mechanism of action is identical in each

 37. IP-6 + INOSITOL: It is a derivative of B vitamin Inositol. There is a patented version that has shown maximum benefit. In the laboratory, IP6 Inositol have been shown to have consistent and reproducible anti-cancer action against a wide range of cancer models (eg. breast, colon, leukemia, liver, lung,  lymphoma, prostate, sarcoma etc) making it a broad-spectrum anti-cancer agent. This anti-cancer action is both preventive and therapeutic. In a very good article on IP-6 in Natural News Barbara Minton reports that: IP6 works in many ways against cancer. Whether from food or from therapeutic supplemental doses, IP6 works against cancer in several ways. Its ability to act as an intracellular messenger means that it is integral in many cellular activities including:
a) Normalizing the rate of cell growth
When cancer cells lose their control mechanisms, rapid and uncontrolled division of malignant cells is often the result. As IP6 repairs the gene mutations and reestablishes control within the cells, their rate of division is slowed
b) Enhancing natural killer cells
Natural killer cells are white blood cells that help protect against infected or cancerous cells. Research has shown that the higher the amount of natural killer cell activity, the lower the incidence of some cancers. A healthy human produces 500 to 1000 cancer cells daily that need to be identified and disposed of by the body. Natural killer cells and natural cell programming result in the vast majority of these cells being destroyed and removed. However, when the body is under stress, including the stress produced by lack of sleep, natural killer cell population is compromised. When the body is under the ultimate stress of being forced to face a diagnosis of cancer and the terrifying toxic treatments that go with such a diagnosis, the natural killer cell population can be reduced at the time it is most needed. IP6 has been documented and proven to increase natural killer cells at such times.
c) Normalizing cell physiology
Because IP6 is able to restore aspects of normality to the cells, it is able to modulate how a cancer cell expresses itself and how threatening it will be. Experiments have shown that IP6 is able to normalize several aspects of cell physiology in spite of the fact that cancer cells have altered DNA. It was demonstrated in the above noted study that IP6 is able to alter gene expression to restore normality. The more a cell can return to its normal state, the more it loses its malignant characteristics.
d) Increasing tumor suppressor p53 gene activity
DNA contains tumor suppressor genes that inhibit pathways and processes that allow cells to become malignant. The p53 gene acts as a control to prevent genetically damaged or cancerous cells from growing and propagating. If the p53 gene becomes damaged or compromised, cancers can establish themselves more easily. IP6 has been shown to greatly increase the amount of p53 gene activity, up to seventeen times. When augmented by IP6, even the toxic treatments offered by traditional medicine become more effective due to its ability to increase p53 gene activity.
e) Enhancing apoptosis
Apoptosis is the orderly programmed process by which cells naturally die off. The process of apoptosis results in the removal of individual cells without affecting the surrounding cells. It is part of the growth and maintenance of healthy tissues. Cancerous cells do not want to die and are resistive to apoptosis. This is one mechanism of tumor formation. IP6 has been shown to restore cancerous cells to normality to the point where they are able to follow through with their programmed death.
f) Affecting angiogenesis
Angiogenesis is the process by which tumors set up their own blood supply, to assure themselves of getting the nutrients necessary to grow. Once this blood supply is set up, tumor growth spirals as more growth leads to more blood supply creation. IP6 has been shown to inhibit this process, resulting in the starvation of cancer cells.
g) Powerfully chelating heavy metal
Tumor cells use iron as a primary growth factor. According to researchers at Wake Forest University, iron chelators are of value in the treatment of cancer since they act by depleting iron and limiting tumor growth. IP6 binds with iron and escorts it from the body. Because IP6 is naturally found in all human cells, it has the ability to get inside tumor cells and remove their iron.
h) Inhibiting metastasis
IP6 inhibits cancer cell migration and invasion by preventing the adhesion of these cells to extra-cellular matrix proteins. This limited adhesion is very important following surgery and biopsy, as these procedures can cause cancer cells to become dislodged. One reason so many breast cancer patients have lymph nodes containing cancer cells is that the squeezing of the breast by the mammography used in diagnosis can dislodge cancer cells which then migrate to the lymph nodes.
j) Inhibiting inflammation
One key indicator used in predicting the survival rate for a cancer patient is the level of systemic inflammation. Inflammation is like a fire going on in the body that will destroy it if not stopped. IP6 helps stop inflammation through chemical messages that halt the production of pro-inflammatory cytokines.
k) Inhibiting free radical production
IP6 acts as an antioxidant in the body. Antioxidants are known to protect against disease states and aging in general. Antioxidants bind with free radicals rendering them harmless. In their free state, these radicals can damage DNA and leave cells susceptible to mutations that can result in the production of cancerous cells. IP6 is significantly more potent as an antioxidant than green tea.
l) IP6 influences genes to halt colon cancer
In another recent study, more information about the molecular mechanisms through which IP6 acts was revealed. Scientists at the Medical University of Silesia in Poland investigated the influence of IP6 on the expression of genes encoding subunits of NFkappaB and of its inhibitor, IkappaBalpha, in human colorectal cancer cells. The results of their study suggest that IP6 primarily influences p65 and IkappaBalpha expression in colon cancer cells. The amount of activity seen was dependent on the IP6 levels and the amount of time it had been present in the cells.

In a study at the University of Colorado Cancer Center, more specific mechanisms through which IP6 is effective were identified. They found that the two genes activated by IP6, p21 and p27, play a critical role in mediating the anticancer effectiveness of IP6. Following activation of the genes by IP6, they were able to halt tumor growth and promote the appropriate death of cells in a process known as apoptosis. This study was published in the February 2009 edition of Cancer Research. This study follows on the heels of other research from the University of Colorado that evaluated the efficacy of IP6 against prostate tumor growth and progression. Prostate cancer was induced in mice given either water containing IP6 or plain water. The researchers found that IP6 inhibited the progression of the cancer cells and strongly reduced the incidence of adenocarcinoma. This is of high significance because 95% of prostate cancers are adenocarcinomas, meaning the cancer has developed in the lining or inner surface of the gland. The incidences of well-differentiated and poorly differentiated adenocarcinomas in the group fed IP6 were reduced by 44% and 62% respectively. Analysis of the prostate tissue showed a 3.5 fold increase in malignant cell death. This highly significant finding established for the first time that oral IP6 suppresses prostate tumor growth and progression at the stage of abnormal or uncontrolled growth. IP6 is non-toxic and produces no side effect. IP6 is a compound found in beans, whole grains, nuts, seeds, rice and wheat bran, corn, and sesame.
Although the IP6 compound was identified many years ago, it wasn't until the late 1980's that its ability to control the rate of abnormal cell division was discovered. A scientist from the University of Maryland, Dr. Abulkalam Shamsuddin, found that IP6 was able to halt well developed cancers. While most cancer research centered on killing cancer cells, Dr. Shamsuddin proved that IP6 could normalize the sugar production of cancerous cells, thereby altering their gene expression toward a more healthful state. 
Dr. Shamsuddin
This discovery has major implications because cancer cells that are well behaved have far less negative consequences to health. Dr. Shamsuddin's studies have shown that tumor regression takes place in people using 8 grams of IP6 daily for three to four weeks. This is the amount that would be found in 12 ounces of whole kernel corn. One of his studies found that after two weeks the tumors of mice treated three times a week with IP6 were 96 percent smaller than the tumors of mice that did not receive IP6! Populations with diets high in IP6 have lower incidences of cancers of the breast, colon and prostate. Dr. Shamsuddin's laboratory experiments with IP6 have been reproduced and extended by scientists around the world, reconfirming his amazing findings. This study is from Acta Poloniae Pharmaceutica, November through December, 2008.
It seems IP6 obtained from food is bound to protein. Before it can be absorbed by the body, it must be freed from this protein by the enzyme phytase that is present in food and naturally in the intestinal tract. The power of the phytase enzyme is damaging to IP6 and renders much of it inactive and therefore less effective when obtained in this form. Pure IP6 from a supplement is not bound to protein and is easily absorbed intact and able to provide its complete medicinal properties.

38. QUERCETIN: Quercetin is a flavonoid present in many vegetables, fruits and beverages. It is probably second only to curcumin in its potency as an anti-oxidant. It can be used for cancer prevention and therapy. In a study published by Dr. Deng the aim of the study was to observe the effects of quercetin on the proliferation of the breast cancer cell line MCF-7 and the gene expression of survivin. They concluded that Quercetin inhibited the growth of MCF-7 cells and promoted apoptosis by inducing G0/ G1 phase arrest. It also regulated the expression of survivin mRNA in MCF-7 cells, which may be the mechanism underlying its antitumor effect. In another study by Dr. Jeong they wanted to find out whether Quecetin was effective even at low doses. This study proved that the chemopreventive efficacy of a physiologically relevant dose of quercetin can be achievable through the inhibition of cell cycle progression. In another study led by Dr. Lara Gibellini they concluded that Quercetin also exerts a direct, pro-apoptotic effect in tumor cells, and can indeed block the growth of several human cancer cell lines at different phases of the cell cycle. Both these effects have been documented in a wide variety of cellular models as well as in animal models. The high toxicity exerted by Qu on cancer cells perfectly matches with the almost total absence of any damages for normal, non-transformed cells.
Researchers from Rutgers University have published the result of a study in the journal Food and Function that explains a synergistic health-promoting relationship when green tea polyphenols and the flavonoid quercetin. Green tea catechins undergo extensive methylation after ingestion, lowering the effectiveness of the health-promoting compounds to shield against cancer proliferation. Quercetin is a known inhibitor of methylation. The study found that combining quercetin with fresh brewed catechins from green tea increased the cellular adsorption of EGCG four times in lung cancer cells and two times in kidney cancer cells, dramatically increasing the effectiveness of this natural cancer fighting compound in vivo. 
Additionally, quercetin decreased methylation of green tea polyphenols, which would otherwise limit their chemopreventive potential. On study done on lung cancer led by Dr. Yang they
demonstrated that quercetin glucuronides inhibited proliferation through G2/M arrest of the cell cycle and induced apoptosis via caspase-3 cascade in the human lung cancer cell line NCI-H209. Quercetin fights cancer in many ways:
 a) Causing the death of cancer cells. It’s important to note that this does not mean that quercetin actually kills the cancer cell—which can be injurious to the body. Instead, what quercetin does is trigger apoptosis. 
b) Inhibition of cancer cell growth. Acting as a natural chemopreventive agent, studies suggest that quercetin can inhibit the occurrence of new, primary cancers, and halt the progress of existing tumor growth. One of the ways it does this is by blocking the creation of new blood vessels that tumors need to feed new growth. In fact, without angiogenesis, studies have shown that tumors cannot grow more than 1 mm in size. Again, this is basically done by inhibiting the proteins that tumor cells express to signal nearby endothelium cells to create new blood vessels. 
c) Metastatic prevention. By blocking cancer cells from degrading and penetrating the membrane barrier that separates living cells from the nonliving, structural extracellular matrix (ECM) in the body, quercetin has been shown to prevent certain cancers from infiltrating the blood stream and spreading into the surrounding and distant tissue. 
d) Circumventing resistance to chemotherapy or angiogenesis stimulation. Radiation treatments can actually stimulate angiogenesis, but this can be blocked when radiotherapy is administered with polyphenols that inhibit the growth of new blood vessels. Polyphenols represent non-toxic alternatives to synthetic anti-angiogenesis drugs, and may be more effective because they act on multiple (rather than specific) proteins—blocking the tumor cells from producing more proteins in an effort to survive and use other pathways to grow. This multiple-protein effect by polyphenols helps to avoid the risk of drug resistance that often develops in cancer cells. 
e) Enhancing the efficacy of chemotherapy drugs. Many studies have shown that combining natural substances like quercetin with standard chemotherapy drugs not only increases their effectiveness, but does so without producing significant toxicity.
Cancer cells generally have dysfunctional mitochondria that are thought to block chemotherapy drugs from inducing apoptosis. One of the ways that quercetin may boost the effectiveness of chemotherapy is by increasing the permeability of cellular mitochondrial membranes (as demonstrated by in vitro experiments)
Quercetin has shown therapeutic benefits in the following cancers:
Leukemia: Quercetin has been shown to inhibit leukemic T-cells from progressing in humans by stopping the phase of the cell cycle in which the cancer would be able to duplicate itself.
Lung Cancer: In one study, the combination of both apple and onion intake was associated with the reduction of lung cancer by up to 50 percent in men and women!
Breast Cancer: The anticancer properties of quercetin are believed to be a result of several cancer fighting capabilities. Quercetin may suppress the activity of the mutant P53 gene common in breast cancer, which is also responsible for the progression of tumor growth.
Neuroblastoma: Developing nerve cells can become cancerous in children and infants. Quercetin may prevent toxins from creating oxidative damage to these cells during development which can lead to neuroblastoma.
Colon Carcinoma: High dosage amounts of quercetin have also been shown to limit the cancerous cell’s ability to proliferate in the large intestine and cause colon carcinoma.
Som of the other cancers it has shown beneift against are  
Acute lymphoblastic leukemia
Colorectal cancer
Esophageal cancer 
Hepatocellular (liver) carcinoma
Ovarian cancer
Pancreatic cancer
Prostate cancer
Research has shown that only 30-50 percent of ingested food-based quercetin is able to make it through the digestive tract and absorb into the blood stream within 30 minutes. As a result of this lower absorption rate, many holistic doctors will recommend supplementing with about 400-1,200 mg/day. 
Dr. Blaycock's protocol is to take curcumin 500 mg and quercetin 500-1,000 mg and dissolve it in virgil olive oil and have this 3 times a day. 
39. LACTOFERRIN - WHEY:  Lactoferrin a drivative of whey protein and also found in human breast milk has been widely studied over the last 70 years, and its role in diverse biological functions is now well known and generally accepted by the scientific community. Lactoferrin cytotoxicity against several cancers is reported to occur in distinct ways under different conditions, namely by:
a) cell membrane disruption
b) apoptosis induction 
c) cell cycle arrest
d) cell immunoreaction
NaturalHealth365 reports why’s lactoferrin is a cancer killer? Lactoferrin activates the innate immune system cells like the neutrophils, macrophages and T-cells. These are the first line of defense against harmful pathogens – including cancer cells.Cancer cells have a highly negative membrane charge which attracts lactoferrin, while healthy normal cells have a neutral charge. Lactoferrin is attracted to the cancer cells, attaches to them and triggers a process that kills the cancer cell; as well as blocking angiogenesis – the growth of blood vessels that feed cancer cells. Another key to lactoferrin’s cancer-fighting properties is its amazing ability to bind with iron. It forms a bond with iron that’s 100 times stronger than transferrin – your body’s major iron transport protein. Lactoferrin triggers the production of glutathione, better known as the ‘master’ antioxidant and a powerful substance in the prevention of cancer. Research reveals that this increase in glutathione was responsible for preventing the development of prostate cancer. In addition, a clinical study with cancer patients showed a regression of patient’s tumors when given whey protein at concentration levels of 30 grams per day.Glutathione is classified as a phase II enzyme. These enzymes are compounds, which carry out many life enhancing functions on a cellular level.Paul Talalay, M.D. of John Hopkins says over 20 years of research confirms that raising the levels of phase II enzymes proves to be a highly effective way to protect against carcinogenesis – the development of new cancer. He says whey supplementation should be considered a cost effective way to both prevent and dismantle cancer. Researchers, at Lund University in Sweden, reported that alpha-lactalbumin proteins found is whey solid have the ability to kill all the known types of breast cancer cells – even at low doses. In fact, their peer-reviewed paper – published in the Journal of Biological Chemistry suggested that when consumed by the body, alpha-lactalbumin is configured into a protein that selectively induces apoptosis (programmed cancer cell suicide) in cancerous tumors.
Many published studies in peer reviewed journals have shown various actions of Lactoferrin on various cancers. Bovine lactoferrin inhibits lung cancer growth through suppression of both inflammation and expression of vascular endothelial growth factor. That study revealed that bLF bovine lactoferrin is an inhibitor of angiogenesis and blocks lung cell inflammation; as such, it has considerable potential for therapeutic use in the treatment of lung cancer. In a breast cancer study it was found that Lactoferrin decreased the cell viability of HS578T and T47D by 47 and 54%, respectively, and increased apoptosis about 2-fold for both cell lines. Proliferation rates decreased by 40.3 and 63.9% for HS578T and T47D, respectively. For the T47D line, cell migration decreased in the presence of the protein. The results gathered in this work suggest that lactoferrin interferes with some of the most important steps involved in cancer development. In a orally administered Bovine Lactoferrin on the Growth of Adenomatous Colorectal Polyps in a Randomized, Placebo-Controlled Clinical Trial of 104 participants 40-75 years age. Ingestion of 3.0-g bLF significantly retarded adenomatous polyp growth in participants 63 years old or younger. In another study on iron-free and iron-saturated bovine lactoferrin inhibit survivin expression and differentially modulate apoptosis in breast cancer it was found that Apo-bLf (iron free) induced significantly greater cytotoxicity and reduction in cell proliferation in both cancer cells showing a time and dose dependent effect. Importantly, no cytotoxicity was detected in normal MCF-10-2A cells. Both forms of bLf significantly reduced cell invasion in cancer cells. Key apoptotic molecules including p53, Bcl-2 family proteins, IAP members and their inhibitors were significantly modulated by both forms of bLf, though differentially in each cell line. Most interestingly, both Apo-bLf and Fe-bLf completely inhibited the expression of survivin protein (key IAP), after 48 h at 30 and 40 nM in cancer cells. It concluded that the capacity of these forms of bLf to target survivin expression and modulation of apoptosis demonstrates an exciting potential for bLf as an anti-cancer therapeutic in the existing void of survivin inhibitors, with a lack of successful inhibitors in the clinical management of cancer. In another study it was found that in a tumor prevention study, a Fe-Lf diet in combination with tamoxifen caused a 4 day delay in tumor formation, and significantly inhibited tumor growth and metastasis to the liver and lung by 48, 58, and 66% (all P < 0.001), respectively, compared to untreated controls. The results indicate that Fe-Lf is a potent natural adjuvant capable of augmenting the chemotherapeutic activity of tamoxifen. It could have application in delaying relapse in tamoxifen-treated breast cancer patients who are at risk of developing ER-negative tumors. A very exciting case study has been reported in Alternative cancer information:Ralph Snyder had the worse case of leukaemia the Mayo Clinic had seen in 20 years. His entire immune system had shut down. His left leg turned black! He was desperate for a Cure…and did whatever his doctors told him to do, including undergoing chemotherapy. Nothing worked. Ralph’s blood counts remained critical. Ralph Snyder needed a miracle––and he found one. His blood counts improved. He gained back every pound his sickness had cost him. His recovery was so unexpected that his oncologist, working out of the world-renowned Mayo Clinic, dubbed him the “Miracle Man.”
That was five years ago. And Ralph is still cancer free!
The natural food that saved Ralph Snyder’s life is lactoferrin.
IMMUNOCAL: a patented speacially prepared whey protein concentrate in phase I-II clinical trials results indicate that whey protein concentrate might deplete tumour cells of GSH and render them more vulnerable to chemotherapy.

40. BREAST MILK + COCONUT OIL - HAMLET + LAURIC ACID:  This is literally Mother Nature's and your Mother's gift to you! Breast milk contains nutrients that have shown startling action against cancer. Lactoferrin another nutrient of breast milk is separately covered above at 39. 

New compounds in breast milk may continue to be dicovered. The other source of one of the key nutrients of breast milk: lauric acid is virgin coconut oil which is 50% composed of it. But the biggest excitement and what will soon be a part of all cancer therapuetic regimen soon is HAMLET  in a study published in the journal PLoS One, the substance, known as "Human Alpha-lactalbumin Made LEthal to Tumor cells" (HAMLET), effectively kills cancer cells. Scientists originally discovered HAMLET on accident while researching the antibacterial properties of human breast milk. Several years later, researchers from Lund University and the University of Gothenburg, both in Sweden, found that HAMLET contains a protein and a fatty acid that contribute to its cancer-fighting effects. And further followup research has revealed that the substance may actually form in the acidic environment of babies' stomachs, the natural byproduct of breast milk consumption. 
"HAMLET is produced by combining alpha-lactalbumin in the milk and oleic acid which is found in babies' stomachs," explained Assistant Professor Roger Karlsson from the University of Gothenburg to the U.K.'s Telegraph about the findings. "So breast feeding has been linked to actually reducing the risk of cancer in babies. HAMLET also triggers some of the cell's apoptotic pathways. HAMLET is a now a new drug candidate with astonishing but well-documented properties. 1) HAMLET kills a broad range of tumor cells but spares healthy, mature cells (Proc. Natl. Acad. Sci, 1995 and 2000). 2) HAMLET kills more than 40 different types of tumour cells, including those most difficult to treat with available drugs. 3) HAMLET kills tumour cells by a natural non-toxic mechanism. Thus, unlike most current cancer drugs, 
HAMLET does not appear to damage healthy tissues. 4) HAMLET occurs naturally in human milk, and may contribute to the lowered cancer incidence in breast-feeding mothers and their children. 5) HAMLET can be produced in large quantities at drug quality. Most of the natural compounds listed above have only reached lab animal studies at the most to showcase the effectiveness against cancer. HAMLET has already shown remarkable results in human trials! HAMLET kills cancer cells by entering the cell’s nucleus and fragmenting the cell’s DNA: Researchers later identified that killer protein as HAMLET and found it could differentiate a normal from a malignant, or tumor, cell. Although it works its way inside the cytoplasm of all cells with which it comes into contact, only in tumor cells does it go beyond the cytoplasm and enter the nucleus (Gustafsson et al., 2005). Once in the nucleus, HAMLET interacts directly with the DNA as well as the proteins (called histones) that surround and package the DNA into chromosomes. The damage HAMLET causes to the cell’s DNA ultimately results in the cell’s death. More specifically, tumor cells exposed to HAMLET undergo programmed cell death, known as apoptosis. HAMLET breaks down the machinery needed for the cell to replicate, leaving the cell with no option but to commit cellular suicide (Gustafsson et al., 2005).  LALBA also is found in cow’s milk, and when it unfolds and combines with oleic acid, it forms a complex known as BAMLET (bovine alpha-lactalbumin made lethal to tumor cells). As its name suggests, BAMLET has been shown to kill several types of cancer cells in the lab and bladder cancer in rat models (Xiao et al., 2013). However, the way it leads to tumor cell death differs from HAMLET; BAMLET destroys the cell’s lysosome (an organelle in the cytoplasm responsible for breaking down cellular waste) rather than the nucleus and thus does not directly interact with DNA or histone proteins (Rammer et al., 2010). Perhaps this difference in target is due to the fact that human LALBA and cow LALBA are not identical proteins (they share approximately 71% of their DNA (Xiao et al., 2013)). This miraculous molecule is a great example of mother nature's kindness. In a study done by University of Adelaide it was discovered that lauric acid killed 93% of the colon cancer cells within 2 days in the lab.

41. WITHAFERIN A (ASHWAGANDHA EXTRACT): Is a 3,000 year old Ayurvedic herb. Interestingly its mechanism of action against cancer is to competitively bind to heat shock protein HSP90 and block it - a key requirement of cancer cascade just like Gedunin listed above. In a study led by Yanke Yu of University of Michigan they found the mechanism of action against cancer as well as tested it efficacy in murine models in pancreatic cancer. They concluded that Withaferin A exhibited potent antiproliferative activity in vitro. WA induced significant apoptosis in Panc-1 cells in a dose-dependent manner. 
Ashwagandha extract Withaferin A
 WA inhibited Hsp90 chaperone activity to induce degradation of Hsp90 client proteins (Akt, Cdk4 and glucocorticoid receptor). WA-biotin binds to C-terminus of Hsp90 which was competitively blocked by unlabeled WA. WA (10 μM) disrupted Hsp90–Cdc37 complexes from 1 to 24 h post-treatment, while it neither blocked ATP binding to Hsp90, nor changed Hsp90–P23 association. WA (3, 6 mg/kg) inhibited tumor growth in pancreatic Panc-1 xenografts by 30% and 58%, respectively. These data demonstrate that Withaferin A binds Hsp90, inhibits Hsp90 chaperone activity through an ATP-independent mechanism, results in Hsp90 client protein degradation, and exhibits in vivo anticancer activity against pancreatic cancer. In another study done at Emory University it was concluded that Withaferin A is a potent breast cancer anti-metastatic agent and the anti-metastatic activity of WFA is, at least in part, mediated through its effects on vimentin and vimentin ser56 phosphorylation. In another study done at University of Kentucky Withaferin A inhibited the activity of heat shock protein (Hsp) 90 as reflected by a sharp increase in Hsp70 expression levels. Hence, we propose that the anti-cancer effects of WA in lymphomas are likely due to its ability to inhibit Hsp90 function and subsequent reduction of critical kinases and cell cycle regulators that are clients of Hsp90. In a study published in PLoS One it was reported that Pharmacological Levels of Withaferin A (Withania somnifera) Trigger Clinically Relevant Anticancer Effects Specific to Triple Negative Breast Cancer Cells. Some of the findings were: pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. They concluded that taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further clinical development to defeat aggressive metastatic breast cancer. In a study done on gasrointestinal carcinoma WA could efficiently block the formation of both CSCs and mCSCs in the UP-LN1 cell line, suggesting that WA may be considered an effective therapeutic agent for this type of GI malignancies. ability to target CSC and mCSC is valuable. In another interesting study done at University of Pittsburg titled Mammary Cancer Chemoprevention by Withaferin A Is accompanied by In Vivo Suppression of Self-Renewal of Cancer Stem Cell they concluded that by an in vivo experiment not only did WA have a cancer preventive action but it was also accompanied by in vivo suppression of breast cancer stem cells (bCSC). WA treatment caused induction of Kruppel-like factor 4 (KLF4) and its knockdown augmented bCSC inhibition, Any non-toxic product that can inhibit the elusive cancer stem cells CSCs is quite valuable. 
WA mechanisms against cancer
 In another peer reviewed study led by Tania Das discovered that
Withaferin A, a withanolide, is the major compound present in leaf extract of the plant which shows anticancer activity against leukemia, breast cancer and colorectal cancer. It arrests the ovarian cancer cells in the G2/M phase in dose dependent manner. Treatment of these cells with this compound leads to apoptosis in a dose dependent manner. It causes the G2/M arrest in both the cell lines. They show that Withaferin A (WA) causes mitotic delay by blocking Spindle assembly checkpoint (SAC) function. They concluded that hat Withaferin A kills cancer cells by delaying the mitotic exit followed by inducing chromosome instability. In a study published in Journal of Cancer Prevention on colon cancer. The researchers found that ound that withaferin-A inhibited the proliferation and migration of HCT116 cells in a concentration-dependent manner. Treatment of HCT116 cells with withaferin-A attenuated interleukin-6-induced activation of STAT3, which has been implicated in the development and progression of colon cancer. To examine the effect of withaferin-A on HCT116 cells proliferation in vivo, we generated HCT116 cells xenograft tumors in Balb/c nude mice and treated the tumor bearing mice with or without withaferin-A intraperitoneally. Treatment with withaferin-A exhibited significant decrease in the volume and weight of tumors as compared to untreated controls.The present study suggests that withaferin-A holds the potential to be developed as a small molecule inhibitor of STAT3 for the treatment of colon cancer. Another study in Scientific Researcher WA inhibited cell viability and induced apoptosis in a concentration- or time-dependent manner on oral cancer cells. In a study titled Anti-cancer Effects and Molecular Mechanisms of Withaferin A led by Seon Min Woo they observed that Withaferin A inhibits cell proliferation, metastasis, invasion, and angiogenesis in cancer cells. Furthermore, it sensitized irradiation, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-, and doxorubicin-mediated apoptosis. The results showed that multiple mechanisms were involved in withaferin A-mediated anti-cancer effects.:
 * First, withaferin A increased intracellular reactive oxygen species (ROS) production and induced ER stress- and mitochondria-mediated apoptosis. 
* Second, withaferin A inhibited the signaling pathways (Jak/STAT, Akt, Notch, and c-Met), which are important in cell survival, proliferation, and metastasis. 
* Third, it induced apoptosis and inhibited cancer cell migration through the up-regulation of prostate apoptosis protein-4 (Par-4). 
* Finally, withaferin A up-regulated pro-apoptotic protein expression levels through the inhibition of proteasome activity
Their findings suggested that withaferin A is a potential, potent therapeutic agent.
Any therapeutic agent which has multiple mechanisms has a greater chance of outwitting cancer plus their ability to reach CSCs also put them in another class. 

42. REBUILDING IMMUNE SYSTEM: The late Dr. Bernard Behari has made himself immortal thanks to the discovery that when naltrexone which is a FDA approved drug used for breaking addictions is given at a low dose of between 3.5 gm to 4.5 mg every night just before sleeping it upregulates an impaired immune system to optimum levels..
Dr. Bernard Behari discoverer of Low Dose Naltrexone

The brief blockade of opioid receptors between 2 a.m. and 4 a.m. that is caused by taking LDN at bedtime each night is believed to produce a prolonged up-regulation of vital elements of the immune system by causing an increase in endorphin and enkephalin production. Normal volunteers who have taken LDN in this fashion have been found to have much higher levels of beta-endorphins circulating in their blood in the following days.
In human cancer, research by Zagon over many years has demonstrated inhibition of a number of different human tumors in laboratory studies by using endorphins and low dose naltrexone. It is suggested that the increased endorphin and enkephalin levels, induced by LDN, work directly on the tumors' opioid receptors — and, perhaps, induce cancer cell death (apoptosis). In addition, it is believed that they act to increase natural killer cells and other healthy immune defenses against cancer. In people with diseases that are partially or largely triggered by a deficiency of endorphins (including cancer and autoimmune diseases), or are accelerated by a deficiency of endorphins (such as HIV/AIDS), restoration of the body's normal production of endorphins is the major therapeutic action of LDN. Olle Melander, MD, and colleagues, from Lund University in Malmo, Sweden, sought an answer to the question of whether enkephalins (opioids made in the body) had any protective effect on the development of breast cancer. In two large studies, enkephalins were measured in fasting plasma samples ‪in thousands of women. The convincing answer was a resounding “YES!”. The lower one’s enkephalins, the higher one’s risk of developing breast cancer! The results were published recently in the oncologists' “bible”, the Journal of Clinical Oncology.‬ ‪LDN doubles of triples enkephalins (endorphins) circulating in the body. In Dr. Behari's practice he found LDN benefitial in the following cancers:

  • Bladder Cancer
  • Breast Cancer
  • Carcinoid
  • Colon & Rectal Cancer
  • Glioblastoma
  • Liver Cancer
  • Lung Cancer (Non-Small Cell)
  • Lymphocytic Leukemia (chronic)
  • Lymphoma (Hodgkin's and Non-Hodgkin's)
  • Malignant Melanoma
  • Multiple Myeloma
  • Neuroblastoma
  • Ovarian Cancer
  • Pancreatic Cancer
  • Prostate Cancer (untreated)
  • Renal Cell Carcinoma
  • Throat Cancer
  • Uterine Cancer
I am true beleiver that a immune system at optimum levels is a key to prevention and cure of cancers. After a few rounds of chemo our immune system is shattered. LDN could help rebuild it within very few days. Impaired immune system plays a role in multitude of diseases and therefore I am a fan of Dr. Behari for having found such a safe and easy to take therapy to repair the immune system. 

43. RSPO1: Intensive chemoradiation regimens used to treat advanced, metastatic cancers can induce significant and often lethal injury in tissues such as the gastrointestinal tract. This damage also becomes a cause of death of the patient.  In a valuable study done by researchers at University of Michigan lab mice were exposed lethal doses of chemo.
Human RSPO1 Gene Expression validated Image fluorescent signal detected by fluorescence microsc
A few mice that survived this were protected by RSPO1 (R-SPONDIN-1). They reported that RSPO1 repaired the damagd tissues by increasing the expression of intestinal stem cells without diluting the effectiveness of the chemo against tumors. Combined SLIT2 and RSPO1 treatment synergistically protected LGR5+ ISCs from chemotherapy-induced depletion, potentiated intestinal regeneration, and prolonged the survival of mice receiving lethal chemotherapy or irradiation. This protective effect required ROBO1 expression and did not enhance intestinal tumor formation or diminish the sensitivity of tumor cells to chemotherapy. These results suggest that adjuvant RSPO1 and SLIT2 (gene) may promote intestinal tissue repair following aggressive chemoradiation by inducing adult stem cells. In an earlier study RSPO1 was founf to preotect oral mucosa from chemoradiation. They discovered that prophylactic treatment with RSpo1 dose-dependently overcame the reduction of basal layer epithelial cellularity, mucosal thickness, and epithelial cell proliferation in tongues of mice exposed to whole-body irradiation. RSpo1 administration also substantially alleviated tongue mucositis in the oral cavity of mice receiving concomitant 5-fluorouracil and x-ray radiation. Furthermore, RSpo1 significantly reduced the extent of tongue ulceration in mice receiving a single fraction, high dose head-only radiation in a dose-dependent manner. Moreover, combined therapy of RSpo1 and keratinocyte growth factor resulted in complete healing of tongue ulcers in mice subjected to snout-only irradiation. In conclusion, their results demonstrate RSpo1 to be a potent therapeutic agent for oral mucositis by enhancing basal layer epithelial regeneration and accelerating mucosal repair through up-regulation of Wnt/beta-catenin pathway. These studies open a new path to cancer patients that need to undergo intesive chemoradiative therapies. They can use RSPO1 as an adjuvant therapy which will induce stem cells to repair tissue damage especially intestinal tracts which regulates immunity and which in turn may allow them to go for higher dose of chemoradiation to ensure death of all proliferating cancer cells. 

44. BERBAMINE - BBD24: Berbamine comes from a plant that has been used for centuries in traditional Chinese medicine to treat inflammation. In recent years, however, the anticancer potential of berbamine and some of its chemical cousins has come to scientists’ attention.
Wendong Huang Ph.D., associate professor in City of Hope's Division of Molecular Diabetes Research, and his colleagues recently published the findings in the journal Molecular Cancer Therapeutics. They found that berbamine and one of its derivatives, called bbd24, blocked the growth of liver cancer cells and drove them to their deaths. Perhaps more important, they also found that the compounds interfered with the malignant stem cells that give rise to liver cancer. Mounting evidence shows that these cancer stem cells are the source of tumor recurrence following surgery and other treatments that do away with the original liver tumor. They also are the likely source of chemotherapy-resistant liver cancers. In a study published by Zheijiang University on The Effects of Berbamine Derivative BBD24 on the Growth in Vitro and in Vivo of Human Osteosarcoma and Corresponding Molecular Mechanisms they observed that BBD24 can significantly inhibit MNNG / HOS xenograft tumor of BALB / c-nu / nu nude mice without any visible toxicity. This study shows that the Berberis amine derivatives BBD24 of has shown significant  in vitro and in vivo anti-osteosarcoma role. In another study done by Yantai University titled Suppression of human lung cancer cell growth and migration by berbamine
their results have shown that BER significantly suppressed the in vitro and ex vivo growth of A549 cells in dose- and time-dependent manners. BER dose-dependently down-regulated the expression of anti-apoptotic protein Bcl-2 and up-regulated the level of pro-apoptotic protein Bax. BER significantly inhibited the A549 cell migration at the low concentrations without restraining the cell growth. Their findings suggest that BER may have the wide therapeutic and/or adjuvant therapeutic application in the treatment of human NSCLC (lung cancer). In a study published by Shailendra Kapoor he surmissed that the past few years have seen the increasing application of berbamine as an anti-cancer agent in other systemic malignancies besides chronic myeloid leukemia. For instance, berbamine administration alters the Bcl-2/Bax ratio and mitigates cell migration and thereby augments the anti-proliferative ability of trichostatin A in non-small cell lung cancers (Duan et al., 2010). Similarly, berbamine inhibits p65 translocation, up-regulates A20 and increases the activation of the GADD45/c-Jun N-terminal kinase (JNK) pathway, thereby enhancing cellular apoptosis in multiple myelomas (Liang et al., 2009a; 2009b). Similarly, alteration of the nuclear factor-kappa B (NF-κB) pathway results in enhanced apoptosis in lymphomas (Du et al., 2010). Similarly, the apoptotic ability of chemotherapeutic agents such as doxorubicin and carmofur is markedly enhanced by co-administration of berbamine, as a result of attenuated expression of cdc2/p34 and vascular endothelial growth factor (VEGF) in affected cells (Cheng et al., 2006; Wang S. et al., 2009; Liu et al., 2010). This results in accentuated G2/M cell cycle arrest and reversal of multidrug resistance in MCF-7/ADR breast cancer tissue (Liu et al., 2010). Similarly apoptosis in hepatocellular carcinomas is augmented by berbamine-mediated induction of the Fas apoptotic pathway and loss in mitothondrial trans-membrane potential (Wang G.Y. et al., 2007; 2009). The above examples clearly illustrate the significant anti-proliferative activity of berbamine.

  45. APOPTIN: Apoptin, a small protein from chicken anemia virus, has attracted great attention, because it specifically kills tumor cells while leaving normal cells a review led by Marek Los published in Elsevier summarize recent discoveries of apoptin's mechanism of action that might provide intriguing insights for the development of novel tumor-selective anticancer drugs 

Proposed mechanism of action of apoptin in tumor cells. Upon heterologous ...

The diagram above describes the proposed mechanism of action of apoptin in tumor cells. Upon heterologous expression or administration of cell-permeable constructs, apoptin associates with the regulatory subunit of PI3K resulting in its constitutive activation, which leads to the sustained activation and nuclear translocation of Akt. The nuclear Akt activates CDK2 by both direct phosphorylation and indirect mechanisms including the proteasome-dependent degradation of p27Kip1. The activated CDK2 phosphorylates apoptin at Thr-108 and thereby enforces its nuclear accumulation in cancer cells. In the nucleus, apoptin can associate with different interaction partners including DEDAF, Nmi, APC/C and PML. A still unknown apoptin-triggered event results in the phosphorylation of Nur77 and its nuclear export. In the cytoplasm Nur77 is known to modulate Bcl-2 proteins, for instance by converting Bcl-2 from an anti-apoptotic to a proapoptotic molecule. This and additional events might induce apoptin-triggered apoptosis by the mitochondrial pathway of caspase activation. The tumor-selective cell death by apoptin has now been demonstrated in a great number of tumor cells using various techniques including adenoviral transfer, transient overexpression or introduction of cell-permeable apoptin constructs. Furthermore, several groups have studied the effect of apoptin in different mouse modes. While all these studies confirmed a tumor-specific effect, the most challenging issue is still the development of efficient delivery forms of apoptin at the tumor lesion. Noteborn and colleagues developed a strategy for the use of apoptin in cancer therapy based on adenoviral vectors. A single injection of the apoptin-producing adenovirus in xenografted hepatomas resulted in a considerably delay in tumor growth. Furthermore, in order to increase the transduction efficiency some studies have investigated other viruses. A recent study, for instance, showed that infection with a replication-deficient fowlpox virus containing the apoptin gene resulted in a significant induction of apoptosis in hepatoma cells and, moreover, efficiently repressed the growth of subcutaneous tumors in mice. Systemic administration of the apoptin gene via the asialoglycoprotein receptor into mice bearing hepatocarcinomas resulted in significant tumor regression, whereas normal hepatocytes were clearly not affected by apoptin gene delivery. In conclusion, further investigations of apoptin and related proteins with a tumor-specific proapoptotic activity will be important not only for understanding the process of carcinogenesis, but might eventually result in new therapeutic options for anticancer treatment.

IN VITRO SUCCESS: There are many natural nutrients which have shown in vitro success in the lab. SInce this would be too early stage and has not yet been tried on actual human cancers in xenograf lab mice it does not get a full listing above but at the same time since the lab studies have been done by reputed researchers and have a logical basis for the results they need to be mentioned here. Also as they are all originating from Nature's bounty all of us can consider them for preventive and cancer patients can consider adding them in their daily diet or list of supplements after checking with their doctor and verifying the safety, contra-indications and dosage. One would need to look up on the web for the studyto find out about the extract name and effective dosage. Listed in no particular order:

+ Bromelain 
+ Sage 
+ okra lectin 
+ galangal root extracts 
+ wild artichoke extract 
+ saffron 
+ blood orange oil 
+ Sesame seeds 
+ Sacred Fig 
+ Evening Primrose 
+ Marjoram 
+ green onion 
+ Kava 
+ Fenugreek extract 
+ Physallis fruit extract 
+ Licorice extract 
+ Lime juice 
+ Apple cider 
+ nuts 
+ apple compound pentameric 
+ cranberries 
+ sweet potato 
+ sweet potato greens 
+ Parsely 
+ Winter Squash 
+ ripened goat cheese exract 
+ Onion extract 
+ maple syrup 
+ Cucurmosin pumpkin extract 
+ Triterpene Pumpkin extract 
+ Olve oil + MK615 extract of Apricot 
+ strawberry extract 
+ Jujube extract 
+ bitter melon juice 
+ black pepper 
+ Garden cress extracts 
+ hydroxytyrosol olive oil extract 
+ Chocolate compound 
+ red dragon fruit skin extract 
+ mung bean sprout extract 
+ Graviola (sursop) 
+ Neoxanthyn extract spinach 
+ Eugenol clove oil 
+ Dandelion extract 
+ Stevioside Stevia compound 
+ Thyme oil 
+ Cinnamon extract 
+ Sillbinin Milk Thistle compound 
+ Garcinol compound of Garcinia Cambogia 
+ purple sweet potato 
+ Isoliquiritgenin compound of licorice 
+ Chlorella hotwater extract 
+ moringa oleifera leaves hot water extract 
+ bassicaphenanthrene compound of turnip 
+ nigela sativa black cumin seeds 
+ Green barley grass extract 
+ aloe vera extract 
+ peach compounds 
+ vitamin K1 kale 
+ Pomegranate 
+ Spirulina extract 
+ Persin compound of avocado. 

When time permitting I will try and add the extracts and compounds referred to in these studies.  
DRUGS FROM NATURAL PRODUCTS: In a comprehensive, integrative and well researched study of Natural Products against cancer published in Cancer Journal by Du J, Tang XL. and called Natural products against cancer: A comprehensive bibliometric study of the research projects, publications, patents and drugs. J Can Res Ther 2014;10:27-37 quite a few interesting facts come out.

Figure 3: FDA drug approvals by year in the field of natural products against cancer. Source: (1) Pharmaceutical Research and Manufacturers of America. PhRMA Annual Membership Survey, 1996-2014; (2) <i>Nature Reviews Drug Discovery</i>. 2014, 13: 85-89; (3) <i>J Nat Prod</i>. 2012, 75, 311-35; 4) <i>Front Chem</i> 2014, 2, 20

Figure 2: Number of publications (source: PubMed), patents (source: Derwent Innovation Index), NIH research grants (source: NIH RePORTER) and NSFC research grants (source: by year in the field of natural products against cancer
For those who are interested find below a list of Drugs from Natural Products and their stage:
Active indications, highest status of drugs (launched or phase 3 only)
In following format:
Drug Name 
Originator company 
Active indications 
Highest status

Pharmaceuticals Ltd
Australia Myelogenous leukemia; Hematological neoplasm;
Myelodysplastic syndrome

Eribulin mesylate
Eisai Co Ltd India
Bladder tumor; Breast tumor; Hormone refractory prostate
cancer; Metastatic breast cancer; Non-small-cell lung
cancer; Prostate tumor; Sarcoma

University of Illinois USA
Breast tumor; Lung tumor; Ovary tumor; Pancreatic ductal
adenocarcinoma; Peritoneal tumor; Prostate tumor; Soft
tissue sarcoma

Ingenol mebutate
Peplin Inc Norway
Basal cell carcinoma; Keratosis; Squamous cell carcinoma Launched
Exenatide Amylin
Pharmaceuticals Inc
USA Myocardial infarction; Non-insulin dependent diabetes;

Mitsui Norin Co Ltd Japan
Basal cell carcinoma; Condyloma; Keratosis;
Papillomavirus infection

Yakult South Korea
Brain tumor; Breast tumor; Colorectal tumor; Lung tumor;
Metastatic colorectal cancer; Metastatic pancreas cancer;
Non-Hodgkin lymphoma; Ovary tumor; Solid tumor;
Squamous cell carcinoma; Stomach tumor; Uterus tumor

Docetaxel Rhone-Poulenc
Rorer Inc England
Breast tumor; Cancer; Endometrioid carcinoma; Esophagus
tumor; Head and neck tumor; Hormone refractory prostate
cancer; Metastatic breast cancer; Metastatic non small cell
lung cancer; Metastatic stomach cancer; Non-small-cell
lung cancer; Ovary tumor; Stomach tumor

Fujisawa Pharmaceutical Co Ltd Japan
Advanced solid tumor; Cutaneous T-cell lymphoma;
Multiple myeloma; Non-Hodgkin lymphoma; Non-small-cell
lung cancer; Peripheral T-cell lymphoma

National Cancer Institute USA
Angiosarcoma; Breast tumor; Cancer; Esophagus tumor;
Germ cell and embryonic cancer; Head and neck tumor;
Kaposis sarcoma; Lung tumor; Metastatic breast cancer;
Non-small-cell lung cancer; Ovary tumor; Stomach tumor;
Testis tumor; Uterine cervix tumor; Uterus tumor

Luye Pharma Group Ltd Singapore
Breast tumor; Non-small-cell lung cancer; Ovary tumor;
Solid tumor

Dexa Medica Group Indonesia
Breast tumor

Conjugated estrogens
Wyeth USA
Breast tumor; Dyspareunia; Hormone dependent prostate
cancer; Hot flashes; Menopause; Postmenopausal

Pharmagenesis Inc Canada
Cachexia; Fatigue; Ischemic stroke; Stroke;
Thrombocytopenic purpura

Hefei Everlife
Pharmaceutical Co Ltd Peoples R China
Metastatic breast cancer; Myelodysplastic syndrome;
Non-small-cell lung cancer

Microbio Co Ltd Taiwan

Immunex Corp USA
Acute myelogenous leukemia; Breast tumor; Cancer;
Hormone refractory prostate cancer; Liver tumor; Multiple
sclerosis; Non-Hodgkin lymphoma

Zeria Pharmaceutical Co Ltd Japan
Leukopenia; Uterine cervix tumor Launched
DLBS-3233 Dexa Medica Group Indonesia Non-insulin dependent diabetes; Polycystic ovary

Boanmycin hydrochloride
Chinese Academy of Medical Sciences, Peoples R China
Head and neck tumor; Lung tumor; Squamous cell

Feron Toray Industries Inc Japan
Astrocytoma; Glioblastoma; Hepatitis B virus infection;
Hepatitis C virus infection; Medulloblastoma; Melanoma

alfa N Center for Genetic Engineering and Biotechnology Thailand
Cancer; Viral infection

Sophoridine hydrochloride
Tonghua Fangda Pharmaceutical Co Ltd Peoples R China

Lentinan viral
Ajinomoto Co Inc Japan
Stomach tumor

Omacetaxine mepesuccinate
Chinese Academy of Medical Sciences Peoples R China
Chronic myelocytic leukemia

Zinostatin stimalamer
Yamanouchi Pharmaceutical Co Ltd Japan
Liver tumor

Saint Petersburg State University Russia
-2 infection; Hepatitis B virus infection; Hepatitis C
virus infection

Kaken Pharmaceutical Co Ltd Japan
Uterine cervix tumor

Microbio Co Ltd Taiwan
Colorectal tumor; Neutropenia
Phase 3

Fosbretabulin(iv, cancer), OXiGENE
Arizona State University USA
Colorectal tumor; Diabetes mellitus; Head and neck tumor;
Lung tumor; Neuroendocrine tumor; Non-small-cell lung
cancer; Ovary tumor; Prostate tumor; Solid tumor; Thyroid
tumor; Uterine cervix tumor
Phase 3

G and E Herbal Biotechnology Co Ltd Thailand
Condyloma; Keratosis; Verruca vulgaris
Phase 3

Estetrol (oral, contraception/hormone deficiency)
Pantarhei Bioscience BV Netherlands
Atrophic vaginitis; Breast tumor; Contraception;
Endometriosis; Hormone deficiency; Migraine;
Osteoporosis; Prostate tumor
Phase 3

PGG Biothera USA
Cancer; Chronic lymphocytic leukemia; Colorectal tumor;
Metastatic colorectal cancer; Non-Hodgkin lymphoma;
Non-small-cell lung cancer
Phase 3

Paclitaxel (oral, Lipfokor, cancer),
DAE HWA/Atebion Korea Institute of Science and Technology South Korea
Metastatic stomach cancer
Phase 3

APH-703 (iv, Alzheimer’s disease)
Aphios Corp USA
Alzheimers disease
Phase 3

Paclitaxel (iv emulsion, TOCOSOL), Sorrento Therapeutics
OncoGenex Pharmaceuticals Inc France
Bladder tumor; Breast tumor; Colorectal tumor;
Non-small-cell lung cancer; Ovary tumor; Solid tumor
Phase 3

PharmaMar SA Spain
Acute lymphoblastic leukemia; Cancer; Melanoma; Multiple
myeloma; Myelofibrosis; Solid tumor; T‑cell lymphoma
Phase 3

Note: One can search each Natural Drug by name to learn more about it and to find out whether it would be useful to a patient you know. Drugs derived from Natural Products typically are expected to have lower side effects and damage to healthy cells.