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http://dx.doi.org/10.4062/biomolther.2008.16.4.336

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

Chae, Ah-Reum (College of Pharmacy, Chung-Ang University)
Shim, Jae-Ho (College of Pharmacy, Chung-Ang University)
Chun, Young-Jin (College of Pharmacy, Chung-Ang University)
Publication Information
Biomolecules & Therapeutics / v.16, no.4, 2008 , pp. 336-342 More about this Journal
Abstract
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 ${\mu}M$ and 16.6 ${\mu}M$, respectively. However, piceatannol did not inhibit CYP1A2 activity in the concentration of up to 100 ${\mu}M$. 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 $\alpha$-naphthoflavone ($\alpha$-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.
Keywords
Cytochrome P450; Enzyme inhibition; Resveratrol; Piceatannol;
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