THE RIMINOPHENAZINE AGENTS CLOFAZIMINE AND B669 REVERSE ACQUIRED MULTIDRUG-RESISTANCE IN A HUMAN LUNG-CANCER CELL-LINE

The potential of the riminophenazine agents clofazimine and B669, at t herapeutically relevant concentrations, to reverse P-glycoprotein-medi ated 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 an d cyclosporin A at minimally cytotoxic concentrations of 1, 0.5 and 5 pg/ml, respectively, were equally effective in restoring sensitivity t o vinblastine, doxorubicin, daunorubicin and mitomycin C in the H69/LX 4 cell line, All three chemosensitising agents also increased the accu mulation of [C-14]vinblastine by H69/LX4 cells. Riminophenazines, whic h are relatively non-toxic, non-carcinogenic and non-myelosuppressive agents, are promising contenders for evaluation in experimental and cl inical oncology as modulators of acquired MDR.