Reversal of daunorubicin resistance in P388/ADR cells by itraconazole

J Clin Invest. 1991 Apr;87(4):1467-9. doi: 10.1172/JCI115154.


Itraconazole is a recently developed triazole antifungal agent that inhibits cell membrane sterol biosynthesis. Itraconazole, in a dose-dependent manner, enhanced intracellular accumulation of daunorubicin and reversed the drug resistance in murine leukemia P388/ADR cells. In addition, itraconazole corrected the altered plasma membrane potentials of P388/ADR cells. The concentrations of itraconazole that reversed drug resistance are comparable to the plasma levels achieved by therapeutic dosage used in the treatment of fungal infections. Therefore, itraconazole is a potential candidate for in vivo use to reverse multidrug resistance in cancer with added benefit of its antifungal property.

MeSH terms

  • Animals
  • Cell Line
  • DNA / biosynthesis
  • Daunorubicin / metabolism
  • Daunorubicin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Resistance*
  • In Vitro Techniques
  • Itraconazole
  • Ketoconazole / analogs & derivatives*
  • Ketoconazole / pharmacology
  • Membrane Potentials / drug effects
  • Mice


  • Itraconazole
  • DNA
  • Ketoconazole
  • Daunorubicin