Abstract 2235: Epigallocatechin-gallate suppresses tumorigenesis by directly targeting Pin1.

Abstract

Abstract The most active anticancer component in green tea is epigallocatechin-3-gallate (EGCG). The human peptidyl prolyl cis/trans isomerase (Pin1) plays a critical role in oncogenic signaling. Herein, we report the X-ray crystal structure of the Pin1/EGCG complex resolved at 1.9 Å resolution. Notably, the structure revealed the presence of EGCG in both the WW and PP1ase domains of Pin1. The direct binding of EGCG with Pin1 was confirmed and the interaction inhibited Pin1 PP1ase activity. In addition, proliferation of cells expressing Pin1 was inhibited and tumor growth in a xenograft mouse model was suppressed. The binding of EGCG with Arg17 in the WW domain prevented the binding of c-Jun, a well-known Pin1 substrate. EGCG treatment corresponded with a decreased abundance of cyclin D1 and diminution of TPA-induced AP-1 or NFκB promoter activity in cells expressing Pin1. Overall, these results showed that EGCG directly suppresses the tumor promoting effect of Pin1. Citation Format: Darya V. Urusova, Jung-Hyun Shim, Dong Joon Kim, Sung Keun Jung, Tatyana Zykova, Andria Carper, Ann M. Bode, Zigang Dong. Epigallocatechin-gallate suppresses tumorigenesis by directly targeting Pin1. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2235. doi:10.1158/1538-7445.AM2013-2235