Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 16 No. 4 • April 2013

Important Advance in Cancer Treatment:
Restoring Activity of Tumor Suppressor Genes
No FDA Approval Required!

A very recent paper1 reports the exciting news that curcumin, a yellow pigment derived from the curry spice turmeric, has been shown to reactivate several hyper­methyl­ated (turned off) tumor suppressor genes in lung, colon, prostate, and breast cancer cells. One of the most common causes of cancer is loss of one or more key tumor suppressor genes, which can occur as a result of mutation, but also by another process, DNA hyper­methyl­ation.

Too little DNA methylation (hypomethylation) can result in the activation of oncogenes that promote cancer, whereas excessive DNA methylation (hypermethylation) can silence tumor suppressor genes that would otherwise inhibit the development of cancer. When tumor suppressor genes are hypermethylated, they are prevented from being expressed. Unlike mutations, however, DNA hypermethyl­ation can be reversed by dietary methylation inhibitors for chemoprevention and also chemotherapy.1

A new paper1 now reveals in vitro and in vivo evidence in mice that curcumin can reactivate the tumor suppressor gene RASSF1A in breast cancer cells, resulting in significant activity against tumor growth. Another paper2 reports that “RASSF1A methylation has the potential to be an ideal cancer biomarker as it occurs at moderate to high frequency in a very wide range of tumour types, yet is comparatively rarely found in normal tissues.” The same paper2 also reports that “RASSF1A promoter methyl­ation has been demonstrated in epithelial hyperplasia and intraductal papillomas of the breast, as well as cancerous epithelium, suggesting that RASSF1A methylation is an early event in breast tumourigenesis.” RASSF1A methyl­ation has also been suggested to be an early event in thyroid tumouri­genesis, childhood neoplasia, and endometrial carcino­genesis.2 In lung cancer, RASSF1A methylation as a diagnostic marker has been investigated and found to occur in ~34% of NSCLC (non-small cell lung cancer) tumors, accompanied by methylation in the corresponding serum.2

Another paper3 describes curcumin as a “potent DNA hypomethylation agent” and explains how the authors understand curcumin to restore the activity of deactivated tumor suppressor genes. The authors of this paper3 note that two nucleoside analogs (azanucleosides) with hypomethylating activity (decitabine or 5-azacytidine) have been approved by the FDA for the treatment of myelodysplastic syndrome, but that, although the results are encouraging, these drugs can be very toxic (by suppressing bone marrow). Curcumin, on the other hand, has been shown to be well tolerated in three different phase 1 clinical trials of up to 12 grams a day.3B The authors3 found that curcumin and one of its major metabolites, tetrahydrocurcumin, are effective in inhibiting hypermethylation induced by DNMT1 (a DNA methyltransferase). Using a leukemia cell line, the global DNA methylation of MV4-11 cells remained unchanged at 1.0 μM curcumin, but decreased about 15–20% at 3.0 and 30.0 μM curcumin compared to the untreated basal methylation level of the cell line.

A paper4 with the same lead author as paper #3 who is also the last author of paper #1 reports that the sesquiterpene lactone parthenolide, the principal bioactive sesquiterpene lactone of the herb feverfew, reactivated the tumor suppressor gene HIN-1 by inhibiting DNA methyltransferase 1 (DNMT1) and thus is an agent of DNA hypomethylation.

Finally, an earlier paper5 reported that EGCG, a major polyphenol in green tea, was effective in inhibiting DNA methyltransferase and reactivating methylation-silenced tumor suppressor genes in cancer cell lines.

What these results suggest is that cancer prevention could be enhanced, perhaps very significantly, by taking hypomethylation agents such as these in safe doses and that their use (possibly together with standard chemotherapy, which is often effective in cancer patients that do not have silenced tumor suppressor genes) could markedly improve chances of survival for these patients who, in the absence of reactivating their silenced tumor suppressor genes may have a dismal prognosis.

Another advantage of using safe natural products for the treatment of cancer is that, provided no claims are made for their efficacy in the treatment of cancer, they do not have to receive FDA approval for sale in the marketplace and, hence, do not require a doctor’s prescription and are generally relatively inexpensive. However, that makes you responsible for your own health in a really major way, so be sure to work with a knowledgeable physician if you choose to use these substances to treat your cancer, as there may be very little in the way of clinical data on their use (correct dosages are usually difficult to predict from animal studies). There is nothing that can replace a physician with a lot of experience, who follows the natural products scientific literature, and who has good diagnostic skills. Also avoid, as much as possible, doctors who are tied up in knots by bureaucratic political rules and regulations (e.g., Medicare, Medicaid, Obama­care) that may (though they may not want to admit it even to themselves) make it impossible for them to use their best judgment in treating their patients.

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