Resveratrol, a natural phenolic compound, inhibits cell proliferation and prevents oxidative DNA damage

Resveratrol (3,4 ' ,5-trihydroxystilbene) is a naturally occurring phenolic compound which is present at high levels in wine and has been recently pro posed as a potential cancer chemopreventive and chemoterapeutic agent. In t his study, we evaluated the antiproliferative activity of resveratrol on a panel of cell lines of various histogenetic origin, including normal rat fi broblasts and mouse mammary epithelial cells compared to human breast, colo n and prostate cancer cells. The concentration of resveratrol inhibiting ce ll growth by 50% (IC50) ranged from about 20 to 100 muM. At such concentrat ion, we were unable to detect a significant increase in the apoptotic index in most of the cell lines analyzed. We also studied the effects of resveratrol on cell cycle distribution. The most striking effect was a reduction in the percentage of cells in the G2/M phase which was most frequently associated with an increase of cells in th e S phase of the cell cycle. We also found that resveratrol is able to prev ent the increase in reactive oxygen species (ROS) following exposure to oxi dative agents (i.e. tobacco-smoke condensate (TAR) and H2O2). Resveratrol a lso reduced nuclear DNA fragmentation, as assessed by single cell gel elect rophoresis (comet test). Taken together our results suggest that resveratro l can act as an antimutagenic/anticarcinogenic agent by preventing oxidativ e DNA damage which plays a pivotal role in the carcinogenic activity of man y genotoxic agents. (C) 2001 Elsevier Science B.V. All rights reserved.