Synthetic triterpenoid methyl-2-cyano-3, 12-dioxooleana-1, 9(11)-dien-28-oate (CDDO-Me) has been shown as a promising agent against ovarian cancer. However, the underlying mechanism is not well understood. Here, we demonstrate that CDDO-Me directly interacts with Hsp90 in cells by cellular thermal shift assay. CDDO-Me treatment leads to upregulation of Hsp70 and degradation of Hsp90 clients (ErbB2 and Akt), indicating the inhibition of Hsp90 by CDDO-Me in cells. Knockdown of Hsp90 significantly inhibits cell proliferation and enhances the anti-proliferation effect of CDDO-Me in H08910 ovarian cancer cells. Dithiothreitol inhibits the interaction of CDDO-Me with Hsp90 in cells and abrogates CDDOMe induced upregulation of Hsp70, degradation of Akt and cell proliferation inhibition. This suggests the anti-ovarian cancer effect of CDDO-Me is possibly mediated by the formation of Michael adducts between CDDO-Me and reactive nucleophiles on Hsp90. This study identifies Hsp90 as a novel target protein of CDDO-Me, and provides a novel insight into the mechanism of action of CDDO-Me in ovarian cancer cells.
基金：
National Basic Research Program of China
(973 Program) (NO. 2015CB910403,
2013CB910903), National Natural Science
Foundation of China (91313303, 31100980,
81272886), Science and Technology Committee of
Shanghai (11JC1406500, 13431900501,
13ZR1456900).
第一作者机构：[1]Shanghai Jiao Tong Univ, Shanghai Tongren Hosp,Chinese Minist Educ, Fac Basic Med,Key Lab Cell Differentiat & Apoptos, Sch Med,Hongqiao Int Inst Med,Chem Biol Div Shang, Shanghai 200030, Peoples R China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Qin Dong-Jun,Tang Cai-Xia,Yang Li,et al.Hsp90 Is a Novel Target Molecule of CDDO-Me in Inhibiting Proliferation of Ovarian Cancer Cells[J].PLOS ONE.2015,10(7):doi:10.1371/journal.pone.0132337.
APA：
Qin, Dong-Jun,Tang, Cai-Xia,Yang, Li,Lei, Hu,Wei, Wei...&Wu, Ying-Li.(2015).Hsp90 Is a Novel Target Molecule of CDDO-Me in Inhibiting Proliferation of Ovarian Cancer Cells.PLOS ONE,10,(7)
MLA：
Qin, Dong-Jun,et al."Hsp90 Is a Novel Target Molecule of CDDO-Me in Inhibiting Proliferation of Ovarian Cancer Cells".PLOS ONE 10..7(2015)
