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.