Autophagy Suppression Accelerates Apoptosis Induced by Norcantharidin in Cholangiocarcinoma
| Autor: | Xiangcheng Li, Xuanxuan Xiong, Yun Wang, Wangjie Jiang, Hao Guo, Qingzhong Tian, Cunjiang Li |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research Programmed cell death ATG5 Antineoplastic Agents Apoptosis Pathology and Forensic Medicine Cholangiocarcinoma 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Autophagy Humans Inner mitochondrial membrane Cell Proliferation chemistry.chemical_classification Membrane Potential Mitochondrial Reactive oxygen species Norcantharidin biology Cytochrome c General Medicine Bridged Bicyclo Compounds Heterocyclic 030104 developmental biology Oncology chemistry Bile Duct Neoplasms 030220 oncology & carcinogenesis Cancer research biology.protein |
| Zdroj: | Pathology oncology research : POR. 26(3) |
| ISSN: | 1532-2807 |
| Popis: | Norcantharidin is a cantharidin demethylated analog with antitumor effects in many tumors, including cholangiocarcinoma. Autophagy suppression is known to increase chemosensitivity in cholangiocarcinoma. This study aimed to determine whether autophagy suppression accelerates apoptosis induced by norcantharidin in human cholangiocarcinoma cells. The human cholangiocarcinoma cell line QBC939 was incubated in RPMI 1640 medium with or without norcantharidin. Autophagy was induced using HBSS media with Ca2+ and Mg2+ supported by 10 mM HEPES or suppressed by treatment with 3-MA or transfection with siRNA against Atg5. The comparison was drawn between these conditions in mitochondrial membrane potential disturbance, the levels of reactive oxygen species (ROS), apoptotic proteins, and apoptosis. Cholangiocarcinoma cell apoptosis was accelerated by norcantharidin. Autophagy suppression up-regulated norcantharidin’s pro-apoptotic effect, but autophagy induction weakened it. As apoptosis was accelerated, ROS production was up-regulated. Bax protein expression, cytochrome c levels and localization, mitochondrial membrane disturbance, and the levels of caspase-9, caspase-3, and cleaved PARP were higher when autophagy was suppressed, and all of those were down-regulated when autophagy was induced. To sum up, it was found that norcantharidin induced cholangiocarcinoma cell death, and autophagy suppression enhanced the pro-apoptotic action of norcantharidin, which appears to involve the mitochondrial apoptosis pathway activation and ROS generation. |
| Databáze: | OpenAIRE |
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