Lung carcinogenesis: Resveratrol modulates the expression of genes involved in the metabolism of PAH in human bronchial epithelial cells

Studies suggest that resveratrol (trans-3,4',5-trihydroxystilbene), which i s a diphenolic antioxidant found in plants and foods, has cancer chemopreve ntive and chemotherapeutic potential. A lower risk of lung cancer among con sumers of wine compared with consumers of other beverages has been observed , which may be partly attributed to the high content of resveratrol particu larly in red wine. We have studied the effect of resveratrol on the express ion of genes involved in the metabolism of polycyclic aromatic hydrocarbons in the human bronchial epithelial cell line BEP2D, Expression of the cytoc hrome P450 IAI (CYPIAI) and IBI (CYPISI), microsomal epoxide hydrolase (mEH ), and glutathione S-transferase PI (GSTPI) genes was measured by quantitat ive reverse transcriptase polymerase chain reaction. The cells were treated either with benzo[a]pyrene or 2,3,7,8-tetrachlorodibenzo-p-dioxin in the p resence or absence of resveratrol. Resveratrol inhibited both the constitut ive and the induced expression of CYPIAI and CYPISI in a dose-dependent man ner. In contrast, the expression of the mEH gene was increased in response to resveratrol and no change in the expression of GSTPI was found. The alte red gene expression in response to resveratrol was reflected in a reduced o verall level of benzo[a]pyrene metabolism. These data indicate that resvera trol may exert lung cancer chemopreventive activity through altering the ex pression of genes involved in the metabolism of polycyclic aromatic hydroca rbons, resulting in altered formation of carcinogenic benzo[a]pyrene metabo lites in human bronchial epithelial cells. (C) 2001 Wiley-Liss, Inc.