Mechanism of Inhibition of Human Cytochrome P450 1A1 and 1B1 by Piceatannol
- Authors
- Chae, Ah-Reum; Shim, Jae-Ho; Chun, Young-Jin
- Issue Date
- Dec-2008
- Publisher
- KOREAN SOC APPLIED PHARMACOLOGY
- Keywords
- Cytochrome P450; Enzyme inhibition; Resveratrol; Piceatannol
- Citation
- BIOMOLECULES & THERAPEUTICS, v.16, no.4, pp 336 - 342
- Pages
- 7
- Journal Title
- BIOMOLECULES & THERAPEUTICS
- Volume
- 16
- Number
- 4
- Start Page
- 336
- End Page
- 342
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/23544
- DOI
- 10.4062/biomolther.2008.16.4.336
- ISSN
- 1976-9148
2005-4483
- 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 co-expressing 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 IC50 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 Akt-mediated 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.
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