Identification of the Multidrug Resistance-Related Membrane Glycoprotein as an Acceptor for Cyclosporine
| Autor: | Brian M. J. Foxwell, Carmen Rodriguez, Gaetane Woerly, Bernhard Ryffel |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Blotting
Western Drug Resistance Antineoplastic Agents Breast Neoplasms Cyclosporins ATP-binding cassette transporter Pharmacology Cell Line chemistry.chemical_compound Tumor Cells Cultured polycyclic compounds Animals Humans ATP Binding Cassette Transporter Subfamily B Member 1 Ovarian Neoplasms Membrane Glycoproteins biology Binding protein Precipitin Tests Neoplasm Proteins Blot Multiple drug resistance Membrane glycoproteins Phenotype chemistry Cell culture Diazirine biology.protein Female Efflux |
| Zdroj: | Journal of Receptor Research. 11:675-686 |
| ISSN: | 0197-5110 |
| DOI: | 10.3109/10799899109066435 |
| Popis: | The immunosuppressive agent cyclosporine A (CSA) has been shown to reverse multidrug resistance (MDR) in malignant cells. In the present study, a 3H-cyclosporine diazirine analogue (3H-PL-CS) was used to photolabel viable MDR 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. |
| Databáze: | OpenAIRE |
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