title: Role of autophagy in high linear energy transfer radiation-induced cytotoxicity to tumor cells.
abstract: Heavy-ion radiotherapy has a potential advantage over conventional radiotherapy due to improved dose distribution and a higher biological effectiveness in cancer therapy. However, there is a little information currently available on the cellular and molecular basis for heavy-ion irradiation-induced cell death. Autophagy, as a novel important target to improve anticancer therapy, has recently attracted considerable attention. In this study, the effect of autophagy induced by high linear energy transfer (LET) carbon ions was examined in various tumor cell lines. To our knowledge, our study is the first to reveal that high-LET carbon ions could induce autophagy in various tumor cells effectively, and the autophagic level in the irradiated cells increased in a dose- and LET-dependent manner. The ability of carbon ions to inhibit the activation of the PI3K/Akt pathway rose with increasing their LET. Moreover, modulation of autophagy in tumor cells could modify their sensitivity to high-LET radiation, and inhibiting autophagy accelerated apoptotic cell death, resulting in an increase in radiosensitivity. Our data imply that targeting autophagy might enhance the effectiveness of heavy-ion radiotherapy.
authors.affiliation: Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China; Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jin
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Ye
authors.forename: Xiongxiong
authors.initials: X
authors.lastname: Liu
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Furusawa
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Wu
authors.forename: Feifei
authors.initials: F
authors.lastname: Li
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Zheng
authors.forename: Zhongying
authors.initials: Z
authors.lastname: Dai
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001343:Autophagy / Q000528:radiation effects*; D000071186:Beclin-1; D002244:Carbon / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D020450:Heavy Ions; D006801:Humans; D018499:Linear Energy Transfer; D008565:Membrane Proteins / Q000235:genetics; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011836:Radiation Tolerance
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; D002244:Carbon; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C491997:BECN1 protein, human; C477012:MAP1LC3A protein, human
keywords: Apoptosis; PI3K/Akt pathway; autophagy; high-LET radiation; radiosensitivity
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