Sensitization of human melanoma cells to melphalan cytotoxicity by adriamycin and carmustine.
Exposure of cultured human melanoma cells from three different cell lines to Adriamycin and carmustine at non-cytotoxic (micromolar) concentrations results in a rapid, reversible depletion of cellular glutathione; maximal depletion is achieved within 1 h, and glutathione levels recover within 2-3 h. Glutathione depletion is accompanied by an enhancement of the cytotoxic effects of the alkylating agent melphalan, which ranges from 15- to 55-fold. These results suggest that the combination of Adriamycin and carmustine may provide a rational drug combination for the rapid depletion of glutathione from malignant melanoma, thereby sensitizing these tumor cells to alkylating agent cytotoxicity.
Jevtović-Todorović
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Department of Pharmacology, University of Illinois College of Medicine, Chicago 60612.
Guenthner
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TM
Jevtorić-Todorović
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D002330:Carmustine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D004347:Drug Interactions; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008558:Melphalan / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D004317:Doxorubicin; D005978:Glutathione; D008558:Melphalan; D002330:Carmustine