Alpha-tocopherol antagonizes the multidrug-resistance-reversal activity of cyclosporin A, verapamil, GF120918, clofazimine and B669.
The effects of the membrane-stabilizing agent, alpha-tocopherol (25 microg/ml), on the chemosensitizing interactions of cyclosporin A (5 microg/ml), verapamil (2 microg/ml), clofazimine (1 microg/ml), B669 (0.5 microg/ml) and GF120918 (0.015 microg/ml) with a P-glycoprotein-expressing human lung cancer cell line (H69/LX4) have been investigated in vitro. In an assay of cell proliferation, all the chemosensitizing agents restored the sensitivity of H69/LX4 cells to doxorubicin and vinblastine. The inclusion of alpha-tocopherol (25 microg/ml) antagonized the multidrug-resistance (MDR)-modifying activity of all five chemosensitizing agents, effectively preventing restoration of sensitivity to both doxorubicin and vinblastine in H69/LX4 cells.
Van Rensburg
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Department of Immunology, Institute for Pathology, Faculty of Medicine, University of Pretoria, South Africa.
Jooné
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Anderson
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D000166:Acridines / Q000494:pharmacology; D016923:Cell Death; D002991:Clofazimine / Q000031:analogs & derivatives / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D044005:Tetrahydroisoquinolines; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology; D014747:Vinblastine / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
D000166:Acridines; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D014810:Vitamin E; D014747:Vinblastine; C030428:B 669; D016572:Cyclosporine; D014700:Verapamil; D002991:Clofazimine; C083501:Elacridar