Actein induces autophagy and apoptosis in human bladder cancer by potentiating ROS/JNK and inhibiting AKT pathways
| Autor: | Xing Li, Yong Jiao, Jiang Ping Wang, Fei Mao, Xi Jiang, Cheng Yuan Wang, Gang Liu, Zhi Bin Xu, Bing Zhong, Bin Song, Bo Zhan, Lu Ji |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
human bladder cancer autophagy and apoptosis Bladder cancer Cell growth Chemistry AKT Black cohosh Autophagy medicine.disease 03 medical and health sciences ROS and JNK 030104 developmental biology 0302 clinical medicine Oncology Apoptosis 030220 oncology & carcinogenesis Cancer cell medicine Cancer research Actein (ACT) Protein kinase B PI3K/AKT/mTOR pathway Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| DOI: | 10.18632/oncotarget.22274 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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