2. Academic Validation
  3. Albendazole-induced autophagy blockade contributes to elevated apoptosis in cholangiocarcinoma cells through AMPK/mTOR activation

Albendazole-induced autophagy blockade contributes to elevated apoptosis in cholangiocarcinoma cells through AMPK/mTOR activation

  • Toxicol Appl Pharmacol. 2022 Nov 1;454:116214. doi: 10.1016/j.taap.2022.116214.
Qing He 1,  Yingxuan Yin 1,  Xiaowen Pan 1,  Yinjuan Wu 2,  Xuerong Li 3
Affiliations

Affiliations

  • 1 Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory for Tropical Diseases Control of Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China; Provincial Engineering Technology Research Center for Biological Vector Control, Guangzhou 510080, China; China Atomic Energy Authority (CAEA) Center of Excellence on Nuclear Technology Applications for Insect Control, Beijing 100048, China.
  • 2 Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory for Tropical Diseases Control of Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China; Provincial Engineering Technology Research Center for Biological Vector Control, Guangzhou 510080, China; China Atomic Energy Authority (CAEA) Center of Excellence on Nuclear Technology Applications for Insect Control, Beijing 100048, China. Electronic address: wuyinjuan@mail.sysu.edu.cn.
  • 3 Department of Parasitology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; Key Laboratory for Tropical Diseases Control of Ministry of Education, Sun Yat-sen University, Guangzhou 510080, China; Provincial Engineering Technology Research Center for Biological Vector Control, Guangzhou 510080, China; China Atomic Energy Authority (CAEA) Center of Excellence on Nuclear Technology Applications for Insect Control, Beijing 100048, China. Electronic address: xuerong2@mail.sysu.edu.cn.
PMID: 36055539 DOI: 10.1016/j.taap.2022.116214
Abstract

Albendazole (ABZ) is a broad-spectrum Anti-parasitic drug that exhibits antitumor effects against several carcinomas. The effects of ABZ on cholangiocarcinoma (CCA) and its underlying mechanisms are still unclear. Our study aims to investigate the role of ABZ in inducing autophagy-mediated Apoptosis of cholangiocarcinoma cells. The antitumor effects of ABZ were evaluated against CCA cells and HIBEC intrahepatic biliary epithelial cells. Furthermore, the Apoptosis rates, and Autophagy flux in RBE and FRH-0201 cells treated with ABZ were investigated. ABZ inhibited proliferation, induced cell death and Apoptosis in CCA cells in vitro. In vivo, tumors from ABZ- treated BALB/c nude mice were significantly smaller than untreated mice. ABZ also induced the initiation of Autophagy via AMPK/mTOR pathways, resulting in the formation of autophagosome. In addition, ABZ blocked autophagic flux by inhibiting the fusion of autophagosome-lysosome, which increased the apoptotic death of CCA cells. However, the apoptotic death of CCA cells induced by ABZ was reversed by 3-methyladenine (3-MA), an autophagosome formation inhibitor, but increased by chloroquine (CQ), an autophagosome-lysosome fusion inhibitor.Our work provides novel mechanisms for anti-tumor effects of ABZ on CCA, suggesting that ABZ may be used as a potent Autophagy Inhibitor in the treatment of CCA.

Keywords

AMPK/Mtor; Albendazole; Antitumor; Autophagy; Cholangiocarcinoma.

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