title: Telomere-Mitochondrion Links Contribute to Induction of Senescence in MCF-7 Cells after Carbon-Ion Irradiation.
abstract: The effects of carbon-ion irradiation on cancer cell telomere function have not been comprehensively studied. In our previous report cancer cells with telomere dysfunction were more sensitive to carbon-ion irradiation, but the underlying mechanisms remained unclear. Here we found that telomerase activity was suppressed by carbon-ion irradiation via hTERT down-regulation. Inhibition of telomere activity by MST-312 further increased cancer cell radiosensitivity to carbon-ion radiation. hTERT suppression caused by either carbon-ion irradiation or MST-312 impaired mitochondrial function, as indicated by decreased membrane potential, mtDNA copy number, mitochondrial mass, total ATP levels and elevated reactive oxygen species (ROS). PGC-1α expression was repressed after carbion-ion irradiation, and hTERT inhibition by MST-312 could further exacerbate this effect. Lowering the mitochondrial ROS level by MitoTEMPO could partially counteract the induction of cellular senescence induced by carbon-ion radiation and MST-312 incubation. Taken together, the current data suggest that telomere-mitochondrion links play a role in the induction of senescence in MCF-7 cells after carbon-ion irradiation.
authors.affiliation: Department of Heavy Ion Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Gansu Province, China E-mail : zhangh@impcas.ac.cn.
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Miao
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Yi
authors.initials: Y
authors.lastname: Xie
authors.forename: Chao
authors.initials: C
authors.lastname: Sun
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000528:radiation effects*; D004249:DNA Damage / Q000528:radiation effects; D005260:Female; D063193:Heavy Ion Radiotherapy; D006801:Humans; D007124:Immunoenzyme Techniques; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000528:radiation effects*; D008928:Mitochondria / Q000528:radiation effects*; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D059506:Telomere Shortening / Q000528:radiation effects*
chemical_list: D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C509186:TERT protein, human; D019098:Telomerase