Oncotarget

Research Papers:

AMPK activation-dependent autophagy compromises oleanolic acid-induced cytotoxicity in human bladder cancer cells

Yarong Song, Peng Zhang, Yadong Sun, Xuechao Li, Lifeng Chen, Yajun Xiao and Yifei Xing _

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Oncotarget. 2017; 8:67942-67954. https://doi.org/10.18632/oncotarget.18980

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Abstract

Yarong Song1,*, Peng Zhang1,*, Yadong Sun1, Xuechao Li1, Lifeng Chen1, Yajun Xiao1 and Yifei Xing1

1Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

*These authors contributed equally to this work

Correspondence to:

Yifei Xing, email: yifei_xing@163.com

Keywords: bladder cancer, oleanolic acid, autophagy, AMPK, cytotoxicity

Received: October 22, 2016     Accepted: June 16, 2017     Published: July 04, 2017

ABSTRACT

Autophagy is an evolutionarily conserved catabolic process in eukaryotic cells, which allows cells to overcome a wide array of of stresses and has recently been shown to result in drug resistance. This study examined the effect of autophagy on oleanolic acid (OA)-induced cytotoxicity against bladder cancer cells. Our study demonstrated that OA inhibited cell viability, proliferation, and induced apoptosis in bladder cancer lines T24 and EJ. Furthermore, OA induced autophagy in both cell lines by activating AMP-activated protein kinase (AMPK), inhibiting mechanistic target of rapamycin (mTOR) and promoting unc-51 like autophagy activating kinase 1 (ULK1). Moreover, inhibiting autophagy by siRNA to autophagy related 7 (ATG7) or with autophagy inhibitor bafilomycin A1 and 3-methyladenine (3-MA) or AMPK inhibitor dorsomorphin (compound C) promoted OA-induced deaths of bladder cancer cells. In contrast, either autophagy activator rapamycin or AMPK activator acadesine (AICAR) compromised OA-induced anti-cancer effect. Our findings suggested that OA induced protective autophagy through AMPK-mTOR-ULK1 signaling pathway in bladder cancer cells and OA in combination with autophagy inhibitor might be a novel alternative for the treatment of bladder cancer.


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