Effect of glutathione-modulating compounds on hydrogen-peroxide-induced cytotoxicity in human glioblastoma and glioma cell lines.
The relation between the intracellular glutathione (GSH) concentration and hydrogen-peroxide(H2O2)-induced cytotoxicity was investigated. The intracellular GSH concentration in human glioblastoma (T98G, U87MG) and glioma (KG1C) cell lines was one or two orders of magnitude higher than that in a human myelogenous leukemic cell line (HL-60), which showed higher sensitivity to H2O2. Pretreatment of these cell lines with L-buthionine-[S,R]-sulfoximine, which significantly reduced the intracellular GSH concentration, increased their sensitivity against H2O2, whereas pretreatment with N-acetyl-L-cysteine, which did not significantly change the intracellular GSH concentration, only marginally protected the cells from the cytotoxic effect of H2O2. The results suggest that drug sensitivity of tumor cells can be modified by glutathione-modulating compounds.
Iida
M
M
Department of Neurosurgery, School of Medicine, Showa University, Tokyo, Japan.
Sunaga
S
S
Hirota
N
N
Kuribayashi
N
N
Sakagami
H
H
Takeda
M
M
Matsumoto
K
K
D000111:Acetylcysteine / Q000494:pharmacology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005909:Glioblastoma / Q000737:chemistry / Q000473:pathology*; D005910:Glioma / Q000737:chemistry / Q000473:pathology*; D005978:Glutathione / Q000032:analysis; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D019328:Buthionine Sulfoximine; D006861:Hydrogen Peroxide; D005978:Glutathione; D000111:Acetylcysteine