Oncotarget

Research Papers:

Cheliensisin A (Chel A) induces apoptosis in human bladder cancer cells by promoting PHLPP2 protein degradation

Ruowen Zhang, Xun Che, Jingjie Zhang, Yang Li, Jingxia Li, Xu Deng, Junlan Zhu, Honglei Jin, Qinshi Zhao and Chuanshu Huang _

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Oncotarget. 2016; 7:66689-66699. https://doi.org/10.18632/oncotarget.11440

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Abstract

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

Correspondence to:

Chuanshu Huang, email: chuanshu.huang@nyumc.org

Qinshi Zhao, email: qinshizhao@mail.kib.ac.cn

Keywords: Chel A, human bladder cancer, apoptosis, PHLPP2, c-Jun

Received: March 13, 2016     Accepted: August 09, 2016     Published: August 20, 2016

ABSTRACT

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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