Hyperthermia, cyclosporine A and melphalan cytotoxicity and transport in multidrug resistant cells.
The ability of hyperthermia and cyclosporine A to modulate melphalan cytotoxicity and transport processes was investigated in a pleiotropic MDR Chinese hamster ovary cell line (CH(R)C5) and in the drug-sensitive parent line (AuxB1). Cyclosporine A increased cytotoxicity of melphalan in MDR cells, but not in drug-sensitive cells. In MDR cells, hyperthermia caused marked enhancement of melphalan cytotoxicity when cyclosporine A was present. The increased melphalan cytotoxicity in MDR cells was accompanied by changes in membrane permeability to the drug. Cyclosporine A caused an increase in melphalan uptake in MDR cells and a decrease in melphalan efflux out of cells, leading to an overall increase in intracellular drug accumulation. Drug transport processes were not affected by cyclosporine A in drug-sensitive cells.
Averill
D A
DA
Département de Chimie et Biochimie, Université du Québec à Montréal, Canada.
Larrivée
B
B
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000493:pharmacokinetics / Q000494:pharmacology; D001692:Biological Transport; D016466:CHO Cells; D006224:Cricetinae; D016572:Cyclosporine / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D004357:Drug Synergism; D006979:Hyperthermia, Induced; D008558:Melphalan / Q000493:pharmacokinetics / Q000494:pharmacology*
D018906:Antineoplastic Agents, Alkylating; D016572:Cyclosporine; D008558:Melphalan