#A179 Antioxidant Response Element Mediated Induction of NAD(P)H:Quinone Oxidoreductase by p-Tyrosol and Hypoxia. Lijun Xue,1 Zhongchu Jin,1 Weiya Chen,1 Hongjuan LI,1 Dan Xue.2 Dept. of Pathophysiology, Division of Basic Medicine, Zhejiang University College of Medicine,1 Hangzhou, China, Dept. of Orthopaedic Surgery, Second Affiliated Hospital, Zhejiang University College of Medicine,2 Hangzhou, China. NAD(P)H: quinone oxidoreductase (NQO1), a two-electron reductase of quinones, is one of important phase II detoxifying enzymes, which prevents quinones's participation in redox cycling and subsequent generation of reactive oxygen species (ROS). Compounds that induce the synthesis of cytoprotective phase II enzymes have shown promise as cancer chemopreventive agents. In the present study, we synthesized a novel simple phenolic compound termed p-tyrosol, which is major content of Chinese herb Hongjingtian. Based on its chemical structure, we hypothesized that this compound could function as phase II enzyme inducers. Spectrophotometric assay showed that p-tyrosol induced NQO1 specific activity in a concentration-dependent fashion in a cultured human liver cancer cell line, SMMC-7721. These effects were accompanied by cellular proliferation inhibition by p-tyrosol. Moreover, p-tyrosol induced activity of NQO1 correlated well with its mRNA expression. Gel-shift assay showed antioxidant response element (ARE) regulated expression and induction of NQO1 gene in response to p-tyrosol. The increase in NQO1 transcription in response to p-tyrosol suggests that Chinese herb Hongjingtian can stimulate transcription of phase II detoxifying enzyme systems, potentially through an ARE-dependent mechanism. As a new antioxidant, p-tyrosol was further investigated whether it induces NQO1 in coordination with low oxidation. We found that hypoxia enhanced NQO1 activity induced by p-tyrosol. Transcriptional factors NF-kB but not AP-1 were involved in ARE mediated NQO1 induction in response to co-treatment of p-tyrosol and hypoxia. Together, these results suggest that p-tyrosol, alone or in combination with other low oxygen conditions, is a potent candidate as a chemopreventive agent by stimulating cytoprotective phase II detoxifying enzymes and enhancing intracellular defenses against genotoxic agents. [The project was supported by National Natural Science Foundation of China (39970649); and by Natural Science Foundation of Zhejiang Province (301529) ] Frontiers in Cancer Prevention Research, 2003 AACR Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.