title: Differential role of hydrogen peroxide and staurosporine in induction of cell death in glioblastoma cells lacking DNA-dependent protein kinase.
abstract: Various DNA double-strand break repair mechanisms, in which DNA-dependent protein kinase (DNA-PK) has a major role, are involved both in the development and treatment of glioblastoma. The aim of the present study was to investigate how glioblastoma cells responded to hydrogen peroxide and staurosporine (STS) and how such a response is related to DNA-PK. Two human glioblastoma cell lines, M059J cells that lack DNA-PK activity, and M059K cells that express a normal level of DNA-PK, were exposed to hydrogen peroxide or STS. The response of the cells to hydrogen peroxide or STS was recorded by measuring cell death, which was detected by three different methods-MTT, annexin-V and propidium iodide staining, and JC-1 mitochondrial probe. The result showed that both hydrogen peroxide and STS were able to induce cell death of the glioblastoma cells and that the former was mainly associated with necrosis and the latter with apoptosis. Glioblastoma cells lacking DNA-PK were less sensitive to STS treatment than those containing DNA-PK. However, DNA-PK had no significant influence on hydrogen peroxide treatment. We further found that catalase, an antioxidant enzyme, could prevent cell death induced by hydrogen peroxide but not by STS, suggesting that the pathways leading to cell death by hydrogen peroxide and STS are different. We conclude that hydrogen peroxide and STS have differential effects on cell death of glioblastoma cells lacking DNA-dependent protein kinase. Such differential roles in the induction of glioblastoma cell death can be of significant value in selecting and/or optimizing the treatment for this malignant brain tumor.
authors.affiliation: Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, N.T., Hong Kong. gchen@cuhk.edu.hk
authors.forename: G G
authors.initials: GG
authors.lastname: Chen
authors.forename: F L F
authors.initials: FL
authors.lastname: Sin
authors.forename: B C S
authors.initials: BC
authors.lastname: Leung
authors.forename: H K
authors.initials: HK
authors.lastname: Ng
authors.forename: W S
authors.initials: WS
authors.lastname: Poon
mesh_terms: D017209:Apoptosis; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects*; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D009336:Necrosis; D009687:Nuclear Proteins; D016877:Oxidants / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology*
chemical_list: D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D009687:Nuclear Proteins; D016877:Oxidants; D006861:Hydrogen Peroxide; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases; D019311:Staurosporine