Trans-resveratrol modulates the catalytic activity and mRNA expression of the procarcinogen-activating human cytochrome P4501B1

The present study was performed to determine if trans-resveratrol (3,5,4'-t rihydroxy-trans-stilbene) modulates the catalytic activity and gene express ion of cytochrome P450 1B1 (CYP1B1). In vitro, trans-resveratrol decreased human recombinant CYP1B1-catalyzed 7-ethoxyresorufin O-dealkylation activit y, with an IC50 value of 1.4 +/- 0.2 muM (mean +/- SEM). Enzyme kinetic ana lysis indicated that trans-resveratrol inhibited CYP1B1 enzyme activity by a mixed-type inhibition and the apparent K-i was 0.75 +/- 0.06 muM. To dete rmine if trans-resveratrol modulates constitutive CYP1B1 gene expression, c ultured MCF-7 human breast carcinoma cells were treated with trans-resverat rol. As indicated by RT-PCR analysis, treatment of MCF-7 cells with 10 muM trans-resveratrol decreased relative CYP1B1 mRNA levels after 5 h, but not after 1.5 or 3 h, of exposure. trans-Resveratrol treatment at 5, 7.5, 10, o r 20 muM for 5 h produced a concentration-dependent decrease in CYP1B1 mRNA levels. The extent of suppression was similar to 50% at 20 muM concentrati on. The suppressive effect was not a consequence of a toxic response to the compound as assessed by a cell proliferation assay. Overall, our novel fin ding that trans-resveratrol inhibits the catalytic activity and suppresses the constitutive gene expression of CYP1B1 leads to the possibility that th is nutraceutical confers protection against toxicity and carcinogenicity in duced by compounds that undergo CYP1B1-catalyzed bioactivation.