Cyclosporin A and verapamil have different effects on energy metabolism in multidrug-resistant tumour cells |
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| Authors: | H J Broxterman H M Pinedo G J Schuurhuis J Lankelma |
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| Affiliation: | Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands. |
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| Abstract: | 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-state 3H-cyclosporin A accumulation at 37 degrees 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. |
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