title: Alpha-tocopherol antagonizes the multidrug-resistance-reversal activity of cyclosporin A, verapamil, GF120918, clofazimine and B669.
abstract: 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.
authors.affiliation: Department of Immunology, Institute for Pathology, Faculty of Medicine, University of Pretoria, South Africa.
authors.forename: C E
authors.initials: CE
authors.lastname: Van Rensburg
authors.forename: G
authors.initials: G
authors.lastname: Jooné
authors.forename: R
authors.initials: R
authors.lastname: Anderson
mesh_terms: 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*
chemical_list: D000166:Acridines; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; D014810:Vitamin E; D014747:Vinblastine; C030428:B 669; D016572:Cyclosporine; D014700:Verapamil; D002991:Clofazimine; C083501:Elacridar