Difloxacin reverses multidrug resistance in HL-60/AR cells that overexpress the multidrug resistance-related protein (MRP) gene.
In this study, we have examined the in vitro chemosensitizing activity of difloxacin, a quinolone antimicrobial agent, in the multidrug-resistant human myeloid leukemia HL-60/AR cell line. HL-60/AR cells were found to overexpress multidrug resistance-associated protein (MRP) mRNA as compared to HL-60 cells. Difloxacin, in a concentration-dependent manner, increased the sensitivity of HL-60/AR cells to daunorubicin, adriamycin, and vincristine, and partially corrected the altered drug transport. In addition, difloxacin corrected subcellular distribution of adriamycin by inducing redistribution of the drug from the perinuclear region to the nucleus in HL-60/AR cells. The chemosensitizing effect of difloxacin was observed at clinically achievable concentrations. We conclude that difloxacin is an effective chemosensitizer of MRP-associated multidrug-resistant tumor cells and is a potential candidate for clinical use to reverse multidrug resistance.
Division of Basic and Clinical Immunology, University of California, Irvine 92717, USA.
S
S
Gollapudi
F
F
Thadepalli
C H
CH
Kim
S
S
Gupta
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D015152:Blotting, Northern; D002939:Ciprofloxacin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003630:Daunorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D024841:Fluoroquinolones; D015870:Gene Expression; D018922:HL-60 Cells; D006801:Humans; D018613:Microscopy, Confocal; D015363:Quinolones / Q000737:chemistry; D014750:Vincristine / Q000493:pharmacokinetics / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D024841:Fluoroquinolones; D015363:Quinolones; D002939:Ciprofloxacin; D014750:Vincristine; C047225:difloxacin; D004317:Doxorubicin; D003630:Daunorubicin