Scientists at the University of Virginia Health System have discovered how resveratrol, a compound found in grape skins, helps to starve cancer cells by inhibiting the action of a key protein that feeds them. The protein, called nuclear factor- kappa B (NF-kB), is found in the nucleus of all cells and activates genes responsible for cell survival. “We used physiologically-relevant doses of resveratrol and found dramatic effects on human cancer cells,” said Marty Mayo, assistant professor of biochemistry and molecular genetics at U.Va.
Mayo said that the resveratrol in one glass of wine three or four times a week is the right amount to block the protein from feeding cancer cells. Drinking much more than that, however, could stop this affect and, in fact, lead to a greater risk of cancer, he said.
The findings, discovered by Fan Yeung, a postdoctoral fellow at U.Va., are published in the May 20 online edition of the Journal of the European Molecular Biology Organization (EMBO) found at: http://embojournal.npgjournals.com.
Resveratrol is an antioxidant found in a number of plants, including grape skins, raspberries, mulberries and peanuts. Its job in nature is to fight fungus during the rainy season, and it is especially prevalent in grapes used in making red wine. Resveratrol is also sold over-the-counter in the U.S. as a nutritional supplement.
For a number of years, scientists have known that resveratrol acts as an anti-cancer agent, but its role has not been well understood. Mayo and his team demonstrated that cancer cells treated with resveratrol died because they became sensitive to a compound called Tumor Necrosis Factor alpha (TNFa). The U.Va. Health System researchers found that resveratrol initiated a reaction in the NF-kB molecule that caused the cancer cells essentially to self-destruct in a process called apoptosis.
The use of NF-kB inhibitors like resveratrol also has important implications for increasing the effectiveness of cancer therapy. “Researchers are always looking for ways to improve cancer therapy,” Mayo said. “Current studies are using compounds similar to TNFa in conjunction with resveratrol to kill cancer cells.” Clinical trials using this approach in patients are showing encouraging results, Mayo said, and this researchmay explain why this combined therapy is effective.
Previous studies have indicated that resveratrol can play a role to help control atherosclerosis, heart disease, arthritis, and autoimmune disorders. Mayo believes the inhibition of NF-kB may be responsible in those disorders, as well, since NF-kB can control inflammatory responses.
Mayo’s research on resveratrol was funded by grants from the National Cancer Institute and the Paul Mellon Prostate Cancer Institute.