FDA APPROVED PROSCILLARIDIN A CAN BE USED AGAINST CANCER TODAY!
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!
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.
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| Calmodulin |
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!
24 comments:
As always good stuff Akshay
Thank you Paul. I thought to post as this can help cancer patients today with minimal side effects. In fact a side effect is benefit to heart health.
Thank you for nice information, I am sure in near future such natural compounds will be the part of regular cancer therapy. One important point is good bioavailability of these compounds to exhibit therapeutic efficacy, which can be achieved by intelligently designing the formulation; a classic example: Curcumin which is already available and used in cancer treatment along with regular therapy (Brand name: Snec-30).
Thank you Sir for nice information. I am sure in near future natural compounds will be the part of regular cancer therapy. One important point is their dose and good bioavailability to exhibit therapeutic effects, which can be tailored by intelligently designing the formulation. In fact, Curcumin is already available and being used along with regular cancer therapy, a classic example is SNEC-30 formulation. Such natural compounds are a ray of hope for cancer patients.
Thank you Agnivesh. Agree on the bioavailability and on curcumin - covered it in another post Natural Therapies Against Cancer on this blog and also take it myself - I am using G2 liquid.
Hi Akshay.
Is this the one you are referering to: https://www.amazon.in/G2-Curcumin-Turmeric-Extract-Piperine/dp/B01LZ1NAZI?
I truely enjoy your blog!
Thank you. Yes that is the one. I take first thing in the morning empty stomach. Add 2 drops on top of half a teaspoon of expensive organic ghee and take it. Not have any breakfast till 5 to 10 mins after that. I also take transresveratrol with the curcumin and on some days add DIM and Milk Thistle. All of which has synergy with each other to enhance cellular bioavailability.
Hi Paul! saw your over at josh's :) saw your were into totocotrienos.
This one is right down your ally:
http://www.eurekaselect.com/134723/article
Hi paul, saw your over at josh's. youre where looking into tocotrienols:
have you seen this one:
http://www.eurekaselect.com/134723/article
?
Hi Ea
I just read the study and it seems too good to be true, but it's early here and my brain is a little more dense than usual so maybe I'm not understanding this, but it seems to be saying that the combination of toco's with quercetin actually does several very good things:
1. Causes senescence of cancer cells while preventing senescence of normal somatic cells.
2. Act as senolytics to destroy and clear senescent cells that have already formed.
Virtually the perfect scenario,or did I misunderstand the study results?
Now that we're discussing this, and you're the supplement King, critique my regimen if you get a chance.
AM empty stomach: IP6-inositol, Pine Bark ext., pterostilbene, celery seed. Feverfew,, Boswellia, Gotu Kola, Ashwagandha, Lithium Mg White Willow
LDN
Lunch with ghee avocado and olive oil: Tocotrienols, Curcumin complex, Lutein ,DIM , Pom extract, Milk Thistle, EGCG, Genestein, Astaxanthin, Mg
More at dinner and bed.
Any thoughts are appreciated.
Hi Paul. I like your supplements routine.
I got nothing to add.
Just a few questions why no melatonin at night? and vitamin d3/d2 in the morning? and what about fish oils?
And are you not utilizing metformin and rapamycin? (metformin in my view is looking more and more compelling, AMPK, cancer preventice and the newer studies on DNA Methylation) i am still more hesitant with rapamycin, not because i do not think it does not work, i would just like more data on it.
Hi Akshay.
Thanks for your response! How much transresveratrol do you add? and on days with milk thistle and DIM (new to me, seems very interesting) do you add?
ps. you should take a look at this study (really quite amazing):
Andrographolide reorganise hyperglycaemia and distorted antioxidant profile in streptozotocin-induced diabetic rats. doi: 10.2174/1871525715666171026115248.
Hi Indun you seem to absolutely clued in with all the latest research and supplements. I take 250mg Transresveratrol, 100mg DIM-Plus since it's a patented product ensuring high bioavailability and Milk Thistle 175mg but one can take a little higher dose. My new thing is hunt for synergies :)
I forgot to add I am a big fan of andrographolide and am researching on safety, interactions, dosage and bioavailability. My favourite benefits are that it upregulated Nrf2 which may be a key in anti aging strategy. Secondly it also sustainably upregulates NAD+ (apparently upregulation by NR is not sustainable and tapers off) whereas here it is via NQO-1. I can write an entire post on how many molecular pathways and gene expressions Nrf2 and Andrographolide impact beneficially.
Paul your routine is very very good. Have you considered intermittent hormone replacement - in males DHEA ? Although it has inverse effect vs rapamycin on mTOR so should be taken not more than 25mg on days when you are pumping iron in gym and have eliminated most of rapamycin from the system. It will give a major boost if you have not taken so far. Another one to consider is Glycine - pure form.
Oh and Paul LDN should be taken strictly at night time just before sleeping.
To Akshay, Indun
So here's the rest of the story. I'm convinced that the sun is the best source of so called vitamin D, so I get daily sun exposure and keep my blood level between 50-60ngs.I take resveratrol as part of a grape seed extract with resveratrol, melatonin 10mgs at night, lycopene synergy with API gen in, chamomile, and parsley. I use NR once a week to jack up my NaD+. I use a powdered glycine 3x's a week. Rapamycin 2mg once a week but might change i t to every 10 days due to half life considerations.
I do take androggraphis twice a week.
LDN in the AM due to dreams and the latest data seems to suggest that it doesn't matter.
Oh and about metformin I take berberine with cinnamon instead due to fatigue from metformin.
I should get a dream blood level.
I forgot about vitamin k2
Hi Indun
You mentioned fish oils. I do eat salmon about 4x's per week and used to take fish oil but the study finding high omega-3 levels in the blood of men with aggressive prostate cancer was concerning and never adequately explained.
You also mentioned metformin. I used to take it but stopped it due to fatigue. It seems that all AMPK activators do that to me, even Gynostemma tea. After reading James Watson's excellent review of the drug I may re-start it.
I meant DHEA blood level
To Akshay:
I think the biggest hurdles that we have to overcome is bioavailability, synergism and timing! the study i will post below is concluding that andrographolides BA at 2.67 % and this seems to be the case with most of our phytochemicals. (very low BA)
Regarding NQO-1 i stumbled upon this study:
Sulforaphane and Other Nutrigenomic Nrf2 Activators: Can the Clinician's Expectation Be Matched by the Reality?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4736808/
"In data from studies comparing CD values of well-known phytochemicals, sulforaphane showed the highest potency, with a concentration as low as 0.2 μM required to double the activity of NQO1" (andrographolides posses the 2nd higest CD of the tested substances)
and sulforaphane has a BA of a staggering 80% when you add the antianticarcinogenic properties to this, it just became a must supplement for me.
To Paul:
You are going to live a long time my friend! I agree with you, the sun is most definitely the best soruce of vitamin D, its just that i live in the northern hemisphere (skandinavia) so it is almost impossible for me to get adequate levels of vitD in the winther months. In regards to fish oil, i fully agree that the best way is through actually consuming fish (that's easy in skandinavia) and to add to this i find it hard to find a brand where the fish oil is somewhat not oxidized. How big is your weekly NR dosage Paul?
Sulforaphane happens to be one of my favourite and goes very well with Andrographolide for Nrf2 activation. I would suggest SulforaDex from Evgen - stable form capsule. Indun what do you do? Are you involved in anti aging or anti cancer research?
Hi Indun
I don't about longevity but all of the self experimentation is kind of fun.
I take about 250 mg of niagen in a week. Feel a little edgy if I take more.
To Akshay
I'll check out Sulforadex. I've been growing my own broccoli sprouts and chewing on them.
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