Cytometric analysis of cytotoxicity of polyphenols and related phenolics to rat thymocytes: potent cytotoxicity of resveratrol to normal cells.

The chemopreventive and chemotherapeutic actions of polyphenols and related phenolics have received considerable attention since these compounds induce apoptosis in several types of cancer cells in vitro. A plausible criterion for the use of such compounds is that they should not exert any toxic effect on normal cells. However, information about the toxicity of polyphenols and related phenolics to normal cells is limited. In this study, the effects of polyphenols and related phenolics on rat thymocytes were examined by flow cytometric analysis with appropriate fluorescent probes. The compounds examined in this study were caffeic acid, rosmarinic acid, chlorogenic acid, (+)-catechin, 6-gingerol, sesamol, resveratrol, and eugenol. Of these, resveratrol was the most cytotoxic on rat thymocytes incubated for 24 hrs with 100 microM of this compound. Resveratrol at a concentration of 10 microM or more (up to 100 microM) led to a significant dose-dependent increase in the population of dead cells, shrunken living cells, annexin V-positive cells and cells with hypodiploidal DNA. In the presence of benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD-FMK), a pan-inhibitor of caspases, the resveratrol-induced increase in the population of cells with hypodiploidal DNA was partially inhibited. Overall, it is suggested that resveratrol at a concentration of 10 microM or more induces apoptosis in normal cells as well as cancer cells (previously reported elsewhere). Thus, at concentrations that are suitable for chemopreventive and chemotherapeutic actions, resveratrol may exert a cytotoxic effect on normal cells.