ALPHA-TOCOPHEROL ANTAGONIZES THE MULTIDRUG-RESISTANCE-REVERSAL ACTIVITY OF CYCLOSPORINE-A, VERAPAMIL, GF120918, CLOFAZIMINE AND B669

The effects of the membrane-stabilizing agent, alpha-tocopherol (25 mu g/ml), on the chemosensitizing interactions of cyclosporin A (5 mu g/ ml), verapamil (2 mu g/ml), clofazimine (1 mu g/ml), B669 (0.5 mu g/ml ) and GF120918 (0.015 mu g/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 mu g/ml) antagonized the multidrug-r esistance (MDR)-modifying activity of all five chemosensitizing agents , effectively preventing restoration of sensitivity to both doxorubici n and vinblastine in H69/LX4 cells. (C) 1998 Elsevier Science Ireland Ltd.