Resistance to tetracycline, a hydrophilic antibiotic, is mediated by P-glycoprotein in human multidrug-resistant cells.
Two multidrug-resistant human leukemic CCRF-CEM sublines (CEM/VCR R and CEM/VLB100) were significantly more resistant to tetracycline, a hydrophilic antibiotic, than parental cells (P < 0.001). Verapamil and cyclosporin A completely reversed tetracycline resistance in CEM/VCR R cells, which also accumulated and retained significantly less [3H]tetracycline than CCRF-CEM cells. Like verapamil, addition of tetracycline to CEM/VCR R cells which had achieved steady-state vincristine levels resulted in augmented vincristine accumulation. [3H]Azidopine photoaffinity labelling of CEM/VCR R membrane proteins was inhibited by tetracycline in a dose-dependent manner. Although drugs associated with the multidrug-resistance phenotype are typically hydrophobic compounds, these data suggest that resistance to tetracycline, despite its hydrophilic nature, is mediated by P-glycoprotein in these cell lines.
Kavallaris
M
M
Children's Leukaemia and Cancer Research Centre, Prince of Wales Children's Hospital, Randwick, Sydney, New South Wales, Australia.
Madafiglio
J
J
Norris
M D
MD
Haber
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D001692:Biological Transport; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology*; D004351:Drug Resistance / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology*; D013752:Tetracycline / Q000378:metabolism* / Q000494:pharmacology; D013753:Tetracycline Resistance / Q000502:physiology*; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology*; D014750:Vincristine / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D014750:Vincristine; D016572:Cyclosporine; D014700:Verapamil; D013752:Tetracycline