2. Academic Validation
  3. Loperamide induces protective autophagy and apoptosis through the ROS/JNK signaling pathway in bladder cancer

Loperamide induces protective autophagy and apoptosis through the ROS/JNK signaling pathway in bladder cancer

  • Biochem Pharmacol. 2023 Oct 18:115870. doi: 10.1016/j.bcp.2023.115870.
Jianjian Wu 1,  Qiang Guo 1,  Juntao Li 1,  Hao Yuan 1,  Chutian Xiao 1,  Jianguang Qiu 2,  Qiong Wu 3,  Dejuan Wang 4
Affiliations

Affiliations

  • 1 Department of Urology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China.
  • 2 Department of Urology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China. Electronic address: qiujg@mail.sysu.edu.cn.
  • 3 Occupational Health Surveillance Center, Guangzhou Twelfth People's Hospital, Guangzhou 510620, China. Electronic address: wuqiong20190531@126.com.
  • 4 Department of Urology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China. Electronic address: wangdej@mail.sysu.edu.cn.
PMID: 37863323 DOI: 10.1016/j.bcp.2023.115870
Abstract

Bladder Cancer is one of the most common carcinomas in the human urinary system worldwide. Loperamide, known as an antidiarrheal drug, exerts anti-tumor activities against various cancers. However, the effect of loperamide on bladder Cancer cells remains unclear. Our study aimed to investigate the effect of loperamide on bladder Cancer and explore the underlying mechanisms. We found that loperamide suppressed the proliferation of 5637 and T24 cells in a dose-dependent manner. Loperamide treatment showed both pro-apoptotic and pro-autophagic effects on bladder Cancer cells. Moreover, it was revealed that loperamide induced Reactive Oxygen Species (ROS) accumulation, leading to the activation of c-Jun N-terminal kinase (JNK) signaling pathway. Notably, ROS scavenger N-acetyl-L-cysteine (NAC) and JNK Inhibitor SP600125 effectively attenuated the induction of Autophagy and Apoptosis triggered by loperamide. Finally, blocking Autophagy with CQ could significantly enhance the anti-cancer effect of loperamide both in vitro and in vivo. Overall, these findings demonstrated that loperamide induced Autophagy and Apoptosis through the ROS-mediated JNK pathway in bladder Cancer cells. Our results suggest that the strategy of combining loperamide with Autophagy Inhibitor CQ may provide a therapeutic option for the treatment of bladder Cancer.

Keywords

Apoptosis; Autophagy; Bladder cancer; JNK; Loperamide; Reactive oxygen species.

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