Title: Cheliensisin A (Chel A) induces apoptosis in human bladder cancer cells by promoting PHLPP2 protein degradation.
Authors: Zhang, Ruowen; Che, Xun; Zhang, Jingjie; Li, Yang; Li, Jingxia; Deng, Xu; Zhu, Junlan; Jin, Honglei; Zhao, Qinshi; Huang, Chuanshu
Published In Oncotarget, (2016 Oct 11)
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.
PubMed ID: 27556506
MeSH Terms: 3' Untranslated Regions/genetics; Apoptosis/drug effects*; Autophagy/drug effects; Base Sequence; Beclin-1/metabolism; Cell Line, Tumor; Epoxy Compounds/pharmacology*; Gene Expression Regulation, Neoplastic/drug effects; Humans; JNK Mitogen-Activated Protein Kinases/metabolism; MicroRNAs/genetics; Phosphoprotein Phosphatases/genetics; Phosphoprotein Phosphatases/metabolism*; Phosphorylation/drug effects; Proteolysis/drug effects; Pyrones/pharmacology*; Sequence Homology, Nucleic Acid; Urinary Bladder Neoplasms/genetics; Urinary Bladder Neoplasms/metabolism; Urinary Bladder Neoplasms/pathology