Resveratrol metabolites have an antiproliferative effect on intestinal epithelial cancer cells

Trans-resveratrol (RV) is an active polyphenol with numerous physiological properties including antitumour activity, especially in colon cancer. RV is metabolized in the intestine and then in the liver to sulphated and glucuronidated forms that are exported to target organs. After exerting their effects, they are eliminated in the urine and stools. There are few and contradictory findings on the biological effects of RV metabolites. On the basis of RV metabolism, we selected three metabolites RV 3-O-sulphate, RV 3-O-glucuronide and RV 4'-O-glucuronide, and studied their effects on cell growth inhibition, the cell cycle and apoptosis using human adenocarcinoma cell line (Caco-2 cell) cultures. Our results show that RV metabolites have an antioxidant activity similar to that RV. Moreover, all metabolites inhibited cell growth in a concentration-dependent manner as well as [(3)H] thymidine incorporation. Furthermore, we observed an increase in the percentage of cell in G0/G1 phase induced by RV metabolite treatments, as well as the induction of apoptosis. On the basis of our results we propose, for the first time, that RV metabolites remain active after their biosynthesis, contributing to the health benefits attributed previously only to RV. These metabolites are a potential target for more research into the prevention and treatment of colon cancer.