Reversal of daunorubicin resistance in P388/ADR cells by itraconazole.
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.
Gupta
S
S
Division of Basic and Clinical Immunology, University of California, Irvine 92717.
Kim
J
J
Gollapudi
S
S
D000818:Animals; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D003630:Daunorubicin / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D066298:In Vitro Techniques; D017964:Itraconazole; D007654:Ketoconazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice
D017964:Itraconazole; D004247:DNA; D007654:Ketoconazole; D003630:Daunorubicin