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AMPK‐mTOR‐ULK1 axis activation‐dependent autophagy promotes hydroxycamptothecin‐induced apoptosis in human bladder cancer cells
Author(s) -
Wang Feifan,
Cao Min,
Fan Mengjing,
Wu Hongshen,
Huang Wei,
Zhang Yan,
Hu Zhenghui,
Jin Xiaodong
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29307
Subject(s) - autophagy , ampk , apoptosis , pi3k/akt/mtor pathway , ulk1 , microbiology and biotechnology , activator (genetics) , cancer research , chemistry , cancer cell , protein kinase a , cell cycle , biology , kinase , cancer , biochemistry , receptor , genetics
10‐hydroxycamptothecin (HCPT), a natural plant extract, exerts anticancer capacity. HCPT has been reported to induce apoptosis and autophagy in human cancer cells. The interaction between autophagy and apoptosis induced by HCPT and the molecular mechanism in bladder cancer cells were investigated in this study. Our results confirmed that HCPT suppressed cell viability and migration and caused cell‐cycle arrest in T24 and 5637. Then, we used Z‐VAD(OMe)‐FMK to clarify that apoptosis induced by HCPT was mediated by caspase. Moreover, HCPT boosted autophagy through activating the AMPK/mTOR/ULK1 pathway. Blocking autophagy by 3‐methyladenine, the adenosine monophosphate‐activated protein kinase (AMPK) inhibitor dorsomorphin and siATG7 reversed HCPT‐induced cytotoxicity. Conversely, rapamycin and the AMPK activator AICAR enhanced growth inhibition and cell apoptosis, suggesting that autophagy played a proapoptosis role. Taken together, our findings showed that HCPT‐induced autophagy mediated by the AMPK pathway in T24 and 5637 cell lines, which reinforced the apoptosis, indicating that HCPT together with autophagy activator would be a novel strategy for clinical treatment in bladder cancer.