α-Tocopherol antagonizes the multidrug-resistance-reversal activity of cyclosporin A, verapamil, GF120918, clofazimine and B669

The effects of the membrane-stabilizing agent, α-tocopherol (25 μg/ml), on the chemosensitizing interactions of cyclosporin A (5 μg/ml), verapamil (2 μg/ml), clofazimine (1 μg/ml), B669 (0.5 μg/ml) and GF120918 (0.015 μg/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 α-tocopherol (25 μg/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.