cis-terpenones as an effective chemopreventive agent against aflatoxin B1-induced cytotoxicity and TCDD-induced P450 1A/B activity in HepG2 cells

作者: Qibing Zhou , Hang Xie , Lin Zhang , Jennifer K. Stewart , Xing-Xing Gu

DOI: 10.1021/TX0601307

关键词: Hepatocellular carcinomaCytochrome P450CarcinogenAflatoxinPharmacologyCytotoxicityNatural productChemistryOltiprazCell culture

摘要: Aflatoxin B1 (AFB1) is a potent carcinogen, which can significantly increase the risk of hepatocellular carcinoma development through food contamination. In past decades, chemopreventive agents, such as oltipraz and chlorophyllins, have demonstrated that chemo-intervention an effective approach to reduce hepatotoxicity by AFB1. However, because potential adverse effects these alternative novel mechanism-based agents are needed. We report here cis-terpenones 1-3, were synthesized precursors natural product analogues in our laboratory, showed promising protective against AFB1-induced cytotoxicity HepG2 cells. Chemo-protection was observed with increasing concentrations co-treatment AFB1, no alone. addition, 1-3 at 10 microM effectively inhibited induced cytochrome P450 1A/1B activity 50% cells, indicated EROD assay. 1A/B involved activation many pre-carcinogens highly inducible liver These results suggested terpenones candidates for AFB1 other carcinogenic stimuli.

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