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Telomere-Mitochondrion Links Contribute to Induction of Senescence in MCF-7 Cells after Carbon-Ion Irradiation

Miao, Guo-Ying;Zhou, Xin;Zhang, Xin;Xie, Yi;Sun, Chao;Liu, Yang;Gan, Lu;Zhang, Hong

  • Published : 2016.06.01

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-$1{\alpha}$ 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.

Keywords

Telomere;mitochondrion;senescence;carbon-ion irradiation

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  2. The non-canonical functions of telomerase: to turn off or not to turn off pp.1573-4978, 2018, https://doi.org/10.1007/s11033-018-4496-x
  3. /TERT Pathway by Catalpol Ameliorates Atherosclerosis via Modulating ROS Production, DNA Damage, and Telomere Function: Implications on Mitochondria and Telomere Link vol.2018, pp.1942-0994, 2018, https://doi.org/10.1155/2018/2876350

Acknowledgement

Supported by : National Natural Science Foundation of China