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Oncotarget. 2017 Nov 1;8(68):112498-112515. doi: 10.18632/oncotarget.22274. eCollection 2017 Dec 22.

Actein induces autophagy and apoptosis in human bladder cancer by potentiating ROS/JNK and inhibiting AKT pathways.

Author information

1
Department of Urology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, China.
2
Department of Orthopaedics, Huai'an First People's Hospital, Nanjing Medical University, Huai'an 223300, China.
3
Branch of Raw Material and Natural Products, Far East Biological Products Co. LTD., Nanjing 210009, China.

Abstract

Human bladder cancer is a common genitourinary malignant cancer worldwide. However, new therapeutic strategies are required to overcome its stagnated survival rate. Triterpene glycoside Actein (ACT), extracted from the herb black cohosh, suppresses the growth of human breast cancer cells. Our study attempted to explore the role of ACT in human bladder cancer cell growth and to reveal the underlying molecular mechanisms. We found that ACT significantly impeded the bladder cancer cell proliferation via induction of G2/M cycle arrest. Additionally, ACT administration triggered autophagy and apoptosis in bladder cancer cells, proved by the autophagosome formation, LC3B-II accumulation, improved cleavage of Caspases/poly (ADP-ribose) polymerase (PARP). Furthermore, reduction of reactive oxygen species (ROS) and p-c-Jun N-terminal kinase (JNK) could markedly reverse ACT-induced autophagy and apoptosis. In contrast, AKT and mammalian target of rapamycin (mTOR) were greatly de-phosphorylated by ACT, while suppressing AKT and mTOR activity could enhance the effects of ACT on apoptosis and autophagy induction. In vivo, ACT reduced the tumor growth with little toxicity. Taken together, our findings indicated that ACT suppressed cell proliferation, induced autophagy and apoptosis through promoting ROS/JNK activation, and blunting AKT pathway in human bladder cancer, which indicated that ACT might be an effective candidate against human bladder cancer in future.

KEYWORDS:

AKT; Actein (ACT); ROS and JNK; autophagy and apoptosis; human bladder cancer

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