Mechanism of Inhibition of Human Cytochrome P450 1A1 and 1B1 by Piceatannol

The resveratrol analogue piceatannol (3,5,3',4'-tetrahydroxy-trans-stilbene) is a polyphenol present in grapes and wine and reported to have anti-carcinogenic activities.To investigate the mechanism of anticarcinogenic activities of piceatannol, the effects on CYP 1 enzymes were determined in Escherichia coli membranes coexpressing recombinant human CYP1A1, CYP1A2 or CYP1B1 with human NADPH-P450 reductase.Piceatannol showed a strong inhibition of CYP1A1 and CYP1B1 in a concentration-dependent manner, and IC 50 of human CYP1A1 and CYP1B1 was 5.8 µM and 16.6 µM, respectively.However, piceatannol did not inhibit CYP1A2 activity in the concentration of up to 100 µM.Piceatannol exhibited 3-fold selectivity for CYP1B1 over CYP1A1.The mode of inhibition of piceatannol was non-competitive for CYP1A1 and CYP1B1.The result that piceatannol did not inhibit CYP1B1-mediated α-naphthoflavone (α-NF) metabolism suggests piceatannol may act as a non-competitive inhibitor as well.In human prostate carcinoma PC-3 cells, piceatannol induces apoptosis and prevents Aktmediated signal pathway.Taken together, abilities of piceatannol to induce apoptotic cell death as well as CYP1 enzyme inhibition make this compound a useful tool for cancer chemoprevention.