Natural terpenone analogs as a novel class of chemoprevention agents

TOXI 132

Qibing Zhou, qzhou@vcu.edu1, Lin Zhang1, and Jennifer K Stewart, jstewart@vcu.edu2. (1) Department of Chemistry, Virginia Commonwealth University, 1001 West Main St, Richmond, VA 23284, (2) Department of Biology, Virginia Commonwealth University, Richmond, VA 23284-2012
We report here that cis-terpenones, which were synthesized as the precursors of natural product analogues in our laboratory, showed promising protective effects against aflatoxin B1 (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 effectively inhibited cytochrome P450 activity in HepG2 cells and also in the in vitro enzyme assays. Furthermore, 40 µM hydroxy-cis-terpenone inhibited accumulation of 3H-labeled AFB1 in HepG2 cells by 50%. Subsequent investigations with various transportor inhibitors implied an OAT-like mechanism for AFB1 uptake and that cis-terpenones modulate this transport mechanism. These results suggested that novel terpenones are candidates for the development of novel mechanism-based chemopreventive agents against AFB1 and other carcinogenic stimuli.
 

General Papers
1:00 PM-4:45 PM, Wednesday, August 22, 2007 BCEC -- 258C, Oral

Division of Chemical Toxicology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007