Effects of glutathione depletion using buthionine sulphoximine on the cytotoxicity in mammalian cells and human tumor cells in vitro.
An inhibitor of glutathione biosynthesis, buthionine sulphoximine (BSO), was used to deplete the endogenous thiols in mammalian cells in vitro. In this study, the cytotoxicity of BSO and BSO combined with the hypoxic cell radiosensitizer misonidazole (MISO) was investigated. Both aerobic and hypoxic cytotoxicity of MISO was found to be increased. The concentration of BSO required to reduce the colony forming ability to 50% (Cc) for the chronic cytotoxicity on V79 cells was 0.03 mmol/L under aerobic condition, while the Cc for the acute cytotoxicity on V79 cells under hypoxic and aerobic conditions was 0.4 and 0.5 mmol/L. The growth inhibition rate of human tumor cells K562 and SGC-7901 by BSO was 6.89-26.06% and 12.01-55.69%, respectively. Enhanced cytotoxicity activity was observed when BSO was used in combination with cis-dichlorodiamino Pt(II) or 5-fluorouracil.
Jin
Y Z
YZ
Institute of Radiation Medicine, Shanghai Medical University.
Ding
L
L
Shen
Z F
ZF
Cai
R M
RM
Xu
L M
LM
Yang
J K
JK
Jin
X Q
XQ
Lu
W Q
WQ
Xu
J F
JF
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D019328:Buthionine Sulfoximine; D015687:Cell Hypoxia / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008920:Misonidazole / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D008920:Misonidazole; D005978:Glutathione; D002945:Cisplatin; D005472:Fluorouracil