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!
