title: Caspase-independent cell death mediated by apoptosis-inducing factor (AIF) nuclear translocation is involved in ionizing radiation induced HepG2 cell death.
abstract: Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. The aim of radiotherapy is to eradicate cancer cells with ionizing radiation. Except for the caspase-dependent mechanism, several lines of evidence demonstrated that caspase-independent mechanism is directly involved in the cell death responding to irradiation. For this reason, defining the contribution of caspase-independent molecular mechanisms represents the main goal in radiotherapy. In this study, we focused on the role of apoptosis-inducing factor (AIF), the caspase-independent molecular, in ionizing radiation induced hepatocellular carcinoma cell line (HepG2) cell death. We found that ionizing radiation has no function on AIF expression in HepG2 cells, but could induce AIF release from the mitochondria and translocate into nuclei. Inhibition of AIF could reduce ionizing radiation induced HepG2 cell death. These studies strongly support a direct relationship between AIF nuclear translocation and radiation induced cell death. What's more, AIF nuclear translocation is caspase-independent manner, but not caspase-dependent manner, in this process. These new findings add a further attractive point of investigation to better define the complex interplay between caspase-independent cell death and radiation therapy.
authors.affiliation: Department of Radiation, Cancer Center of Guangdong General Hospital (Guangdong Academy of Medical Science), Guangzhou, 510080, Guangdong, China.
authors.forename: Hengwen
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Physiology, Guangzhou Medical University, Guangzhou, 510182, Guangdong, China.
authors.forename: Shana
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Physiology, Guangzhou Medical University, Guangzhou, 510182, Guangdong, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology, Guangzhou Medical University, Guangzhou, 510182, Guangdong, China.
authors.forename: Yajie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Guangdong Medical College Affiliated Pengpai Memorial Hospital, Hai Feng, 516400, Gungdong, China.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Gao
authors.affiliation: Department of Physiology, Guangzhou Medical University, Guangzhou, 510182, Guangdong, China. Electronic address: zhaoshenting@126.com.
authors.forename: Shenting
authors.initials: S
authors.lastname: Zhao
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000528:radiation effects; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D051033:Apoptosis Inducing Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D061945:Caspase Inhibitors / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D051033:Apoptosis Inducing Factor; D061945:Caspase Inhibitors; D034741:RNA, Small Interfering; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D020169:Caspases
keywords: AIF; Caspase-independent pathway; HepG2; Ionizing radiation