title: The riminophenazine agents clofazimine and B669 reverse acquired multidrug resistance in a human lung cancer cell line.
abstract: The potential of the riminophenazine agents clofazimine and B669, at therapeutically relevant concentrations, to reverse P-glycoprotein-mediated multidrug-resistance (MDR) in a human lung cancer cell line (H69/LX4) has been investigated in vitro. Cyclosporin A, a well-documented MDR-modifying agent, was included for comparison. Clofazimine, B669 and cyclosporin A at minimally cytotoxic concentrations of 1, 0.5 and 5 micrograms/ml, respectively, were equally effective in restoring sensitivity to vinblastine, doxorubicin, daunorubicin and mitomycin C in the H69/LX4 cell line. All three chemosensitizing agents also increased the accumulation of [14C]vinblastine by H69/LX4 cells. Riminophenazines, which are relatively non-toxic, non-carcinogenic and non-myelosuppressive agents, are promising contenders for evaluation in experimental and clinical oncology as modulators of acquired MDR.
authors.affiliation: Department of Immunology, University of Pretoria, South Africa.
authors.forename: C E
authors.initials: CE
authors.lastname: Van Rensburg
authors.forename: R
authors.initials: R
authors.lastname: Anderson
authors.forename: M S
authors.initials: MS
authors.lastname: Myer
authors.forename: G K
authors.initials: GK
authors.lastname: Jooné
authors.forename: J F
authors.initials: JF
authors.lastname: O'Sullivan
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D002250:Carbon Radioisotopes; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002991:Clofazimine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D004347:Drug Interactions; D018432:Drug Resistance, Multiple; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D014747:Vinblastine; C030428:B 669; D016572:Cyclosporine; D002991:Clofazimine