Intracellular glutathione as a determinant of responsiveness to antitumor drugs.
The effect of glutathione depletion on cytotoxicity of the anthracycline daunorubicin, and of a copper:bis-thiosemicarbazone chelate, was examined in the P388 murine leukemia and its anthracycline-resistant subline, P388/ADR. Depletion of intracellular glutathione was accomplished through exposure to buthionine sulfoximine, a specific inhibitor of glutathione synthesis. Cytotoxicity of daunorubicin was not altered by glutathione depletion, while responsiveness to the bis-thiosemicarbazone chelate was thereby enhanced.
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D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D019328:Buthionine Sulfoximine; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000378:metabolism; D003630:Daunorubicin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D009279:Naphthacenes / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D002614:Chelating Agents; D009279:Naphthacenes; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D003300:Copper; D004317:Doxorubicin; D005978:Glutathione; D003630:Daunorubicin