Hsp90 Is a Novel Target Molecule of CDDO-Me in Inhibiting Proliferation of Ovarian Cancer Cells

作者：Qin, Dong-Jun; Tang, Cai-Xia; Yang, Li; Lei, Hu; Wei, Wei; Wang, Ying-Ying; Ma, Chun-Min; Gao, Feng-Hou; Xu, Han-Zhang^*; Wu, Ying-Li

来源：PLos One, 2015, 10(7): e0132337.

DOI：10.1371/journal.pone.0132337

• SHOCK-PROTEIN 90
• TRITERPENOID CDDO
• SYNTHETIC TRITERPENOIDS
• BARDOXOLONE METHYL
• APOPTOSIS
• EXPRESSION
• PREVENTION
• ESTER

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.

• 出版日期2015-7-2
• 单位上海交通大学; 河北医科大学