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

Cancer Lett. 1998 May 15;127(1-2):107-12. doi: 10.1016/s0304-3835(98)00020-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridines / pharmacology
  • Cell Death
  • Clofazimine / analogs & derivatives
  • Clofazimine / pharmacology
  • Cyclosporine / pharmacology
  • Drug Resistance, Multiple*
  • Humans
  • Isoquinolines / pharmacology
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Tetrahydroisoquinolines*
  • Tumor Cells, Cultured
  • Verapamil / pharmacology
  • Vinblastine / metabolism
  • Vitamin E / pharmacology*

Substances

  • Acridines
  • Isoquinolines
  • Tetrahydroisoquinolines
  • Vitamin E
  • Vinblastine
  • B 669
  • Cyclosporine
  • Verapamil
  • Clofazimine
  • Elacridar