Resveratrol inhibits the proliferation of normal human keratinocytes in vitro

Resveratrol, a phytoalexin found in grapes and other plants, is a potent antioxidant, anti-inflammatory, and antiproliferative agent that is thought to have chemopreventive properties with respect to carcinogenesis. However, the antiproliferative effects of resveratrol have been described primarily for cultured tumor cells and its effects on the proliferation of normal cells are not clear. We evaluated the viability and proliferation of cultured normal human keratinocytes (KCs) exposed to resveratrol (0.25-100 muM) for different lengths of time (5-72 h) by means of H-3-thymidine incorporation, direct cell counts, and a tetrazolium-based formazan reaction. The first two methods indicated that resveratrol, even at low concentrations, induced a time-and concentration-dependent inhibition of KC proliferation. However, formazan production was actually increased at moderate resveratrol concentrations (10 muM) and diminished only at higher concentrations. Even brief exposure (5 h) of KCs to resveratrol resulted in a concentration-dependent elevation in formazan production. This was blocked by ionomycin but was not dependent on Ca2+. We conclude that resveratrol, even at submicromolar concentrations, inhibits the proliferation of normal human KCs in vitro and, at higher concentrations (40-100 muM), is cytotoxic to these cells. (C) 2001 Wiley-Liss, Inc.