title: The Protective Roles of ROS-Mediated Mitophagy on125I Seeds Radiation Induced Cell Death in HCT116 Cells.
abstract: For many unresectable carcinomas and locally recurrent cancers (LRC),125I seeds brachytherapy is a feasible, effective, and safe treatment. Several studies have shown that125I 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 that125I 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-1αand its target genes BINP3 and NIX (BINP3L), which subsequently triggered mitophagy. Importantly,125I seeds radiation induced mitophagy promoted cells survival and protected HCT116 cells from apoptosis. These results collectively indicated that125I 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 of125I seeds radiation treatment, which might be of clinical significance in tumor therapy.
authors.affiliation: Department of Radiation Oncology, Peking University 3rd Hospital, Haidian District, Beijing 100191, China; School of Medicine, Anhui University of Science and Technology, Huainan 232001, Anhui, China.
authors.forename: Lelin
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Radiation Oncology, Peking University 3rd Hospital, Haidian District, Beijing 100191, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Peking University 3rd Hospital, Haidian District, Beijing 100191, China.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Radiation Oncology, Peking University 3rd Hospital, Haidian District, Beijing 100191, China.
authors.forename: Junjie
authors.identifier: 0000-0002-4092-2232
authors.initials: J
authors.lastname: Wang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects*; D002867:Chromones / Q000494:pharmacology; D005434:Flow Cytometry; D005720:Gamma Rays; D045325:HCT116 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007457:Iodine Radioisotopes / Q000737:chemistry; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000528:radiation effects; D008565:Membrane Proteins / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000528:radiation effects / Q000648:ultrastructure; D063306:Mitophagy / Q000187:drug effects / Q000528:radiation effects*; D009025:Morpholines / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000528:radiation effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: C116838:BNIP3L protein, human; D002867:Chromones; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007457:Iodine Radioisotopes; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009025:Morpholines; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D025521:Tumor Suppressor Proteins; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C025946:3-methyladenine; D000255:Adenosine Triphosphate; D000225:Adenine