Involvement of intracellular glutathione in induction of apoptosis by cisplatin in a human pharyngeal carcinoma cell line.
We investigated the effect of intracellular glutathione (GSH) levels on apoptosis in KB cells induced by cisplatin (CDDP). The mode of cell death, apoptosis or necrosis, was evaluated by biochemical and morphological criteria. The treatment of KB cells with D,L-buthionine-(S,R)-sulfoximine (BSO, a gamma-glutamyl cysteine synthetase inhibitor) decreased GSH level to 1/7th of that of control cells, and augmented cell death induced by CDDP via a necrotic rather than apoptotic process (the ratio of necrosis to apoptosis; n/a>14). In contrast, treatment with 2-oxothiazolidine-4-carboxylic acid (OTZ, a precursor of cysteine) increased GSH levels 1.7 fold compared with that of untreated cells, inhibited cell death induced by CDDP and switched the mode of cell death from necrosis to apoptosis (n/a<0.8, similar to untreated cells). These results suggest that the GSH level affects the cytotoxicity of CDDP and plays an important role in switching the mode of cell death induced by CDDP.
Sugimoto
C
C
Department of Otolaryngology, Fukui Medical School, Matsuoka-cho, Japan.
Matsukawa
S
S
Fujieda
S
S
Noda
I
I
Tanaka
N
N
Tsuzuki
H
H
Saito
H
H
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D019328:Buthionine Sulfoximine; D002945:Cisplatin / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000187:drug effects; D005978:Glutathione / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives; D009336:Necrosis; D010610:Pharyngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011761:Pyrrolidonecarboxylic Acid; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D013844:Thiazoles; D053778:Thiazolidines; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005978:Glutathione; D002945:Cisplatin; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid