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The Protective Roles of ROS-Mediated Mitophagy on (125)I Seeds Radiation Induced Cell Death in HCT116 Cells

For many unresectable carcinomas and locally recurrent cancers (LRC), (125)I seeds brachytherapy is a feasible, effective, and safe treatment. Several studies have shown that (125)I seeds radiation exerts anticancer activity by triggering DNA damage. However, recent evidence shows mitochondrial qual...

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Detalles Bibliográficos
Autores principales: Hu, Lelin, Wang, Hao, Huang, Li, Zhao, Yong, Wang, Junjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5227180/
https://www.ncbi.nlm.nih.gov/pubmed/28119765
http://dx.doi.org/10.1155/2016/9460462
Descripción
Sumario:For many unresectable carcinomas and locally recurrent cancers (LRC), (125)I seeds brachytherapy is a feasible, effective, and safe treatment. Several studies have shown that (125)I seeds radiation exerts anticancer activity by triggering DNA damage. However, recent evidence shows mitochondrial quality to be another crucial determinant of cell fate, with mitophagy playing a central role in this control mechanism. Herein, we found that (125)I seeds irradiation injured mitochondria, leading to significantly elevated mitochondrial and intracellular ROS (reactive oxygen species) levels in HCT116 cells. The accumulation of mitochondrial ROS increased the expression of HIF-1α and its target genes BINP3 and NIX (BINP3L), which subsequently triggered mitophagy. Importantly, (125)I seeds radiation induced mitophagy promoted cells survival and protected HCT116 cells from apoptosis. These results collectively indicated that (125)I seeds radiation triggered mitophagy by upregulating the level of ROS to promote cellular homeostasis and survival. The present study uncovered the critical role of mitophagy in modulating the sensitivity of tumor cells to radiation therapy and suggested that chemotherapy targeting on mitophagy might improve the efficiency of (125)I seeds radiation treatment, which might be of clinical significance in tumor therapy.