作者: Qibing Zhou , Hang Xie , Lin Zhang , Jennifer K. Stewart , Xing-Xing Gu
DOI: 10.1021/TX0601307
关键词: Hepatocellular carcinoma 、 Cytochrome P450 、 Carcinogen 、 Aflatoxin 、 Pharmacology 、 Cytotoxicity 、 Natural product 、 Chemistry 、 Oltipraz 、 Cell 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.