title: cis-Terpenones as an effective chemopreventive agent against aflatoxin B1-induced cytotoxicity and TCDD-induced P450 1A/B activity in HepG2 cells.
abstract: 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 is an effective approach to reduce hepatotoxicity by AFB1. However, because of the potential adverse effects of these agents, alternative novel mechanism-based chemopreventive agents are needed. We report here that novel cis-terpenones 1-3, which were synthesized as the precursors of natural product analogues in our laboratory, showed promising protective effects against AFB1-induced cytotoxicity in HepG2 cells. Chemo-protection was observed with increasing concentrations of cis-terpenones in the co-treatment of AFB1, and no cytotoxicity was observed with cis-terpenones alone. In addition, cis-terpenones 1-3 at 10 and microM effectively inhibited induced cytochrome P450 1A/1B activity by 50% in HepG2 cells, as indicated by an EROD assay. P450 1A/B is involved in the activation of many pre-carcinogens and is highly inducible in liver cells. These results suggested that novel terpenones 1-3 are candidates for the development of novel mechanism-based chemopreventive agents against AFB1 and other carcinogenic stimuli.
authors.affiliation: Department of Chemistry, Virginia Commonwealth University, 1001 West Main Street, Richmond, Virginia 23284-2006, USA. qzhou@vcu.edu
authors.forename: Qibing
authors.initials: Q
authors.lastname: Zhou
authors.forename: Hang
authors.initials: H
authors.lastname: Xie
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Stewart
authors.forename: Xing-Xing
authors.initials: XX
authors.lastname: Gu
authors.forename: John J
authors.initials: JJ
authors.lastname: Ryan
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018890:Chemoprevention; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D013729:Terpenes / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D002273:Carcinogens; D000072317:Polychlorinated Dibenzodioxins; D013729:Terpenes; D016604:Aflatoxin B1; D019363:Cytochrome P-450 CYP1A1