Resveratrol Suppresses Cancer Stem Cells

Pandey et al. Breast Cancer Res Treat.

Resveratrol is a compound found in grapes, red wine, purple grape juice, peanuts, and berries that has been associated with many health benefits, particularly reduction in heart disease. Some studies have demonstrated that resveratrol increases life span when administered at high concentrations. One area of controversy has been the potential of resveratrol in the treatment of cancer.

One way of testing the anti-cancer efficacy of compounds is to administer the compound of interest to cancer cells that are growing “in a test tube”, or “in vitro.” Recently it was shown that cancer cells taken from a patient and propagated in vitro are usually not representative of the original tumor from which the cancer cells were excised. Specifically, it has been shown that in patients, cancer cells can broadly be classified into the rapidly multiplying cells, and the “sleeping cells” otherwise known as tumor stem cells. It appears that in vitro the rapidly multiplying cells continue multiplying, but the cancer stem cells do not multiply. This is important because the cancer stem cells seem to be the cells responsible for causing the tumor to spread, whereas in the rapidly multiplying cells actually seem to be weaker and more sensitive to chemotherapy.

To date the majority of studies investigating effects of resveratrol on cancer have focused on testing with the rapidly multiplying cells. The paper published today investigated the effects of resveratrol on tumor stem cells. Breast cancer tumor stem cells where isolated based on expression of the proteins CD44 and ESA, and lacking CD24. Tumor stem cells were harvested from patients that were both estrogen receptor positive and negative. It was found that addition of resveratrol caused death of the tumor stem cells, as well as blocked their ability to form three dimensional tumors in tissue culture called “mammospheres.”

Interestingly it seemed like the effects of the resveratrol were mediated by manipulating the way in which the cancer stem cells make fat. Specifically, resveratrol caused a significant reduction in fat synthesis which is associated with down-regulation of the enzyme fatty acid synthase (FAS). The suppression of the enzyme FAS was correlated with upregulation of the genes DAPK2 and BNIP3, which are known to stimulate a process called “apoptosis”, or cellular suicide.

This recent paper belongs to a growing example of scientific reports in which various “treatments” advocated by naturopathic doctors seem to have effects on cancer stem cells. For example, a previous publication (Kakarala et al. Targeting breast stem cells with the cancer preventive compounds curcumin and piperine. Breast Cancer Res Treat. 2010 Aug;122(3):777-85.) reported that the chemical curcumin, which is a component of the Indian spice turmeric, selectively inhibits cancer stem cells.

It appears that many of the chemotherapeutic drugs that are conventionally used in the treatment of cancer do not affect the cancer stem cell because chemotherapy requires tumor cells to be actively proliferating. In contrast, many of the “natural remedies” seem to suppress cancer stem cells because their activities seem to be mediated by other means than the ones in which chemotherapy works. It will be interesting to see if more papers such as the present one appear, which seem to provide scientific rationale for a more “compassionate approach” to cancer therapy

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