Identification of the multidrug resistance-related P-glycoprotein as a cyclosporine binding protein - PubMed (original) (raw)
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- PMID: 2572960
Identification of the multidrug resistance-related P-glycoprotein as a cyclosporine binding protein
B M Foxwell et al. Mol Pharmacol. 1989 Oct.
Abstract
The immunosuppressive agent cyclosporine A has been shown to reverse multidrug resistance (MDR) in malignant cells. In the present study, a 3H-cyclosporine diazirine analogue was used to photolabel viable MDR Chinese hamster ovary cells. The 170-kDa membrane P-glycoprotein, which functions as a drug efflux pump, was strongly labeled. The binding of 3H-cyclosporine diazirine analogue to P-glycoprotein was competable by excess cyclosporine A and by the nonimmunosuppressive cyclosporine H. These results suggest that cyclosporine reverses the MDR phenotype by binding directly to P-glycoprotein and that this binding is not dependent on the immunosuppressive potential of the cyclosporine derivative. The identification of P-glycoprotein as a cyclosporine binding protein has obvious implications for cancer chemotherapy.
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