title: An IDH1 mutation inhibits growth of glioma cells via GSH depletion and ROS generation.
abstract: The isocitrate dehydrogenase 1 (IDH1) gene mutation occurs frequently in glioma. While some studies have demonstrated that IDH1 mutations are associated with prolonged survival, the mechanism remains unclear. In this study, we found that growth was significantly inhibited in glioma cells overexpressing the mutated IDH1 gene. Furthermore, these cells were characterized by decreased intracellular NADPH levels accompanied by glutathione (GSH) depletion and reactive oxygen species (ROS) generation. Moreover, the increased apoptosis and the decreased proliferation were found in the glioma cells overexpressing the mutant IDH1 gene. Accordingly, our study demonstrates that using H2O2-regulated mutant IDH1 glioma cells could obviously increase the inhibition of cell growth; nevertheless, GSH had the opposite result. Our study provides direct evidence that mutation of IDH1 profoundly inhibits the growth of glioma cells, and we speculate that this is the major factor behind its association with prolonged survival in glioma. Finally, our study indicates that depletion of GSH and generation of ROS are the primary cellular events associated with this mutation.
authors.affiliation: Department of Neurosurgery, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, 226001, Jiangsu, People's Republic of China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Shi
authors.forename: Hao
authors.initials: H
authors.lastname: Zuo
authors.forename: Lanchun
authors.initials: L
authors.lastname: Ni
authors.forename: Liang
authors.initials: L
authors.lastname: Xia
authors.forename: Longxiang
authors.initials: L
authors.lastname: Zhao
authors.forename: Mingjie
authors.initials: M
authors.lastname: Gong
authors.forename: Dekang
authors.initials: D
authors.lastname: Nie
authors.forename: Peipei
authors.initials: P
authors.lastname: Gong
authors.forename: Daming
authors.initials: D
authors.lastname: Cui
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Jian
authors.initials: J
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D009154:Mutation; D009249:NADP / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D009249:NADP; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D005978:Glutathione