CYCLOSPORINE-A AND VERAPAMIL HAVE DIFFERENT EFFECTS ON ENERGY-METABOLISM IN MULTIDRUG-RESISTANT TUMOR-CELLS

Cyclosporin A (Sandimmune®) rapidly induced an increase in daunorubicin accumulation in multidrug-resistant human ovarian carcinoma cells (2780AD) and was more potent than verapamil. Steady- state3H-cyclosporin A accumulation at 37°C in 2780AD cells was 60-70% of that in the sensitive A2780 cells. A rapid increase of ATP consumption and lactate production was induced in 2780AD cells by verapamil, but not by cyclosporin A. These results suggest that the interactions of cyclosporin A and verapamil with P-glycoprotein, which leads to inhibition of drug transport, have a different mechanistic basis. © The MacMillan Press Ltd., 1990.