Cheliensisin A (Chel A) induces apoptosis in human bladder cancer cells by promoting PHLPP2 protein degradation
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Ruowen Zhang1,*, Xun Che1,*, Jingjie Zhang1,*, Yang Li1,3, Jingxia Li1, Xu Deng2, Junlan Zhu1,3, Honglei Jin3, Qinshi Zhao2, Chuanshu Huang1
1Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA
2State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China
3Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China
*These authors contributed equally to this work
Chuanshu Huang, email: firstname.lastname@example.org
Qinshi Zhao, email: email@example.com
Keywords: Chel A, human bladder cancer, apoptosis, PHLPP2, c-Jun
Received: March 13, 2016 Accepted: August 09, 2016 Published: August 20, 2016
Cheliensisin A (Chel A), a styryl-lactone compound extracted from Goniothalamus cheliensis, is reported to have significant anti-cancer effects in various cancer cells. Here we demonstrated that Chel A treatment resulted in apoptosis and an inhibition of anchorage-independent growth in human bladder cancer T24, T24T and U5637 cells. Mechanistic studies showed that such effect is mediated by PH domain and Leucine rich repeat Protein Phosphatases (PHLPP2) protein. Chel A treatment led to PHLPP2 degradation and subsequently increased in c-Jun phosphorylation. Moreover PHLPP2 degradation could be attenuated by inhibition of autophagy, which was mediated by Beclin 1. Collectively, we discover that Chel A treatment induces Beclin-dependent autophagy, consequently mediates PHLPP2 degradation and JNK/C-Jun phosphorylation and activation, further in turn contributing to apoptosis in human bladder cancer cells. Current studies provide a significant insight into understanding of anticancer effect of Chel A in treatment of human bladder cancer.
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