@article {Ciolino760, author = {Henry P. Ciolino and Grace Chao Yeh}, title = {Inhibition of Aryl Hydrocarbon-Induced Cytochrome P-450 1A1 Enzyme Activity and CYP1A1 Expression by Resveratrol}, volume = {56}, number = {4}, pages = {760--767}, year = {1999}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {We investigated the effect of resveratrol, a constituent of the human diet that has been shown to inhibit aryl hydrocarbon-induced carcinogenesis in animals, on the carcinogen activation pathway regulated by the aryl hydrocarbon receptor. Resveratrol inhibited the metabolism of the environmental aryl hydrocarbon benzo[a]pyrene (B[a]P) catalyzed by microsomes isolated from B[a]P-treated human hepatoma HepG2 cells. Resveratrol competitively inhibited, in a concentration-dependent manner, the activity of the carcinogen activating enzymes cytochrome P-450 (CYP)1A1/CYP1A2 in microsomes and intact HepG2 cells. Resveratrol inhibited the B[a]P-induced expression of the CYP1A1gene, as measured at the mRNA and transcriptional levels. Resveratrol abolished the binding of B[a]P-activated nuclear aryl hydrocarbon receptor to the xenobiotic-responsive element of theCYP1A1 promoter but did not itself bind to the receptor. Resveratrol was also effective in inhibiting CYP1A1transcription induced by the aryl hydrocarbon dimethylbenz[a]anthracene in human mammary carcinoma MCF-7 cells. These data demonstrate that resveratrol inhibits aryl hydrocarbon-induced CYP1A activity in vitro by directly inhibiting CYP1A1/1A2 enzyme activity and by inhibiting the signal transduction pathway that up-regulates the expression of carcinogen activating enzymes. These activities may be an important part of the chemopreventive activity of resveratrol in vivo. U.S. Government}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/56/4/760}, eprint = {https://molpharm.aspetjournals.org/content/56/4/760.full.pdf}, journal = {Molecular Pharmacology} }