title: Acquisition of radioresistance by IL-6 treatment is caused by suppression of oxidative stress derived from mitochondria after γ-irradiation.
abstract: Interleukin (IL)-6 is a multifunctional cytokine and is one of the radiation-induced bystander factors. This study aimed to clarify the mechanism of acquisition of radioresistance through the control of reactive oxygen species (ROS) by IL-6. We used a rat glioma cell line (C6) as tumor cells and a rat astrocyte cell line (RNB) as non-tumor cells. Our results showed that the surviving fraction of C6 cells after 6 Gy irradiation was increased by the addition of IL-6, but that this was not the case in RNB cells. In addition, the number of 53BP1 foci in C6 cells at 30 min after γ-irradiation were decreased by IL-6. Levels of ROS in whole C6 cells, and superoxide in the mitochondria of C6 cells immediately after γ-irradiation, were reduced by IL-6, but this was not observed in RNB cells. The mitochondrial membrane potential detected by JC-1 in C6 and RNB cells was inhibited by IL-6 alone. Therefore, it was concluded that IL-6 leads specifically to radioresistance in tumor cells by inhibition of increases in ROS after γ-irradiation.
authors.affiliation: Department of Radiology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Tamari
authors.affiliation: Advanced Molecular Imaging Center, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan.
authors.forename: Genro
authors.initials: G
authors.lastname: Kashino
authors.affiliation: Department of Radiology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Mori
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D008401:Gas Chromatography-Mass Spectrometry; D005910:Glioma / Q000473:pathology / Q000532:radiotherapy; D015850:Interleukin-6 / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial; D055432:Metabolomics; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D018384:Oxidative Stress / Q000528:radiation effects; D011836:Radiation Tolerance / Q000187:drug effects* / Q000528:radiation effects*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071857:Tumor Suppressor p53-Binding Protein 1 / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D017382:Reactive Oxygen Species; D000071857:Tumor Suppressor p53-Binding Protein 1
keywords: IL-6; ROS; mitochondria; radioresistance