title: Cheliensisin A (Chel A) induces apoptosis in human bladder cancer cells by promoting PHLPP2 protein degradation.
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.
authors.affiliation: Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.
authors.forename: Ruowen
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.
authors.forename: Xun
authors.initials: X
authors.lastname: Che
authors.affiliation: Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.
authors.forename: Jingjie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.|Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China 325035.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.
authors.forename: Jingxia
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Deng
authors.affiliation: Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.|Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China 325035.
authors.forename: Junlan
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China 325035.
authors.forename: Honglei
authors.initials: H
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650204, China.
authors.forename: Qinshi
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Nelson Institute of Environmental Medicine, New York University School of Medicine, Tuxedo, NY 10987, USA.
authors.forename: Chuanshu
authors.initials: C
authors.lastname: Huang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects; D001483:Base Sequence; D000071186:Beclin-1 / Q000378:metabolism; D045744:Cell Line, Tumor; D004852:Epoxy Compounds / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D011753:Pyrones / Q000494:pharmacology*; D012689:Sequence Homology, Nucleic Acid; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; D000071186:Beclin-1; D004852:Epoxy Compounds; C534612:MIRN31 microRNA, human; D035683:MicroRNAs; D011753:Pyrones; C504861:cheliensisin A; D048031:JNK Mitogen-Activated Protein Kinases; C541572:PHLPP2 protein, human; D010749:Phosphoprotein Phosphatases
keywords: Chel A; PHLPP2; apoptosis; c-Jun; human bladder cancer