Intracellular glutathione levels in human colon cancer cells naturally resistant to cross-linking agents.
Correlation between sensitivity to two cross-linking agents, 1-(4-amino-2-methylpyridine-5-yl)-methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) and cisplatin (DDP), and intracellular glutathione (GSH) level was investigated for two naturally drug-resistant human colon cancer cell lines in comparison with two drug-sensitive human leukemia cell lines. As a result, no appreciable correlation was observed between them. We also studied the possibility that DL-buthionine-S,R-sulfoximine (BSO), an inhibitor of GSH biosynthesis, can sensitize the cancer cells to these anticancer agents via depletion of intracellular GSH. It was found that BSO potentiated ACNU cytotoxicity against human leukemia K562 cells and DDP cytotoxicity against K562 and human colon cancer WiDr cells. It indicates that cancer cells with higher GSH level are more effectively sensitized by BSO regardless of degree of their intrinsic sensitivity to these anticancer agents. These results suggest that intracellular GSH level is not a common mechanism for natural resistance to cross-linking agents in human colon cancer cells but one of the determinants of sensitivity to these anticancer agents of GSH-rich cells.
Ozawa
S
S
Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Tokyo.
Iwata
K
K
Kubodera
A
A
Inaba
M
M
D000963:Antimetabolites / Q000494:pharmacology; D019328:Buthionine Sulfoximine; D002945:Cisplatin / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004351:Drug Resistance; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000378:metabolism; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D015376:Nimustine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000963:Antimetabolites; D003432:Cross-Linking Reagents; D015376:Nimustine; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005978:Glutathione; D002945:Cisplatin