文献类型：期刊文献

英文题名：Deoxyelephantopin inhibits cancer cell proliferation and functions as a selective partial agonist against PPARγ

作者：Zou, Gang[2];Gao, Zhenting[2];Wang, Jidong[1];Zhang, Yu[1];Ding, Hong[1];Huang, Jin[2];Chen, Lili[1];Guo, Yuewei[1];Jiang, Hualiang[1,2];Shen, Xu[1,2]

机构：[1]Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 210203, Peoples R China;[2]E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China

年份：2008

卷号：75

期号：6

起止页码：1381

外文期刊名：BIOCHEMICAL PHARMACOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000254687800014)】；

语种：英文

外文关键词：deoxyelephantopin; PPAR gamma; partial agonist; surface plasmon resonance; molecular docking

摘要：Deoxyelephantopin (ESD) was reported to potentiate apoptosis, inhibit invasion and abolish osteoclastogenesis but no target protein was disclosed. Here, we discovered that ESD could significantly inhibit the proliferation of different cancer cells and induce apoptosis and cell cycle arrest at G(2)/M phase in HeLa cell. Moreover, biochemical and biophysical assays revealed that ESD acted as a specific partial agonist against PPAR gamma. Molecular docking with site-directed mutagenesis analyses indicated that ESD functioned as a partial agonist of PPAR gamma by adopting a distinct binding mode to PPAR gamma compared with rosiglitazone. The PPAR gamma knockdown results indicated that the inhibition of ESD against the cancer cell proliferation is more possibly through PPAR gamma-independent pathway and our findings might supply potent binding features for ESD/PPAR gamma interaction at atomic level, and shed light on the potential acting target information for this natural compound. (c) 2007 Elsevier Inc. All rights reserved.