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The Protective Effects of Mcl-1 on Mitochondrial Damage and Oxidative Stress in Imiquimod-Induced Cancer Cell Death.
Chang, Shu-Hao; Chuang, Kai-Cheng; Li, Zheng-Yi; Chang, Mao-Chia; Liu, Kuang-Ting; Hsu, Chien-Sheng; Huang, Shi-Wei; Chung, Mu-Chi; Wang, Shih-Chung; Chen, Yi-Ju; Shieh, Jeng-Jer.
Afiliación
  • Chang SH; Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402202, Taiwan.
  • Chuang KC; Department of Life Sciences, National Chung Hsing University, Taichung 402202, Taiwan.
  • Li ZY; Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402202, Taiwan.
  • Chang MC; Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402202, Taiwan.
  • Liu KT; Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402202, Taiwan.
  • Hsu CS; Department of Pathology & Laboratory Medicine, Taoyuan Armed Forces General Hospital, Taoyuan 325208, Taiwan.
  • Huang SW; Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402202, Taiwan.
  • Chung MC; Frontier Molecular Medical Research Center in Children, Changhua Christian Children Hospital, Changhua 500209, Taiwan.
  • Wang SC; Center for Cell Therapy and Translation Research, China Medical University Hospital, Taichung 404327, Taiwan.
  • Chen YJ; Division of Nephrology, Department of Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan.
  • Shieh JJ; PhD Program in Translational Medicine, National Chung Hsing University, Taichung 402202, Taiwan.
Cancers (Basel) ; 16(17)2024 Sep 02.
Article en En | MEDLINE | ID: mdl-39272918
ABSTRACT
Mitochondria, vital organelles that generate ATP, determine cell fate. Dysfunctional and damaged mitochondria are fragmented and removed through mitophagy, a mitochondrial quality control mechanism. The FDA-approved drug IMQ, a synthetic agonist of Toll-like receptor 7, exhibits antitumor activity against various skin malignancies. We previously reported that IMQ promptly reduced the level of the antiapoptotic Mcl-1 protein and that Mcl-1 overexpression attenuated IMQ-triggered apoptosis in skin cancer cells. Furthermore, IMQ profoundly disrupted mitochondrial function, promoted mitochondrial fragmentation, induced mitophagy, and caused cell death by generating high levels of ROS. However, whether Mcl-1 protects mitochondria from IMQ treatment is still unknown. In this study, we demonstrated that Mcl-1 overexpression induced resistance to IMQ-induced apoptosis and reduced both IMQ-induced ROS generation and oxidative stress in cancer cells. Mcl-1 overexpression maintained mitochondrial function and integrity and prevented mitophagy in IMQ-treated cancer cells. Furthermore, IL-6 protected against IMQ-induced apoptosis by increasing Mcl-1 expression and attenuating IMQ-induced mitochondrial fragmentation. Mcl-1 overexpression ameliorates IMQ-induced ROS generation and mitochondrial fragmentation, thereby increasing mitochondrial stability and ultimately attenuating IMQ-induced cell death. Investigating the roles of Mcl-1 in mitochondria is a potential strategy for cancer therapy development.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cancers (Basel) Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cancers (Basel) Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Suiza