Resistance to tetracycline, a hydrophilic antibiotic, is mediated by P-glycoprotein in human multidrug-resistant cells. 1993

M Kavallaris, and J Madafiglio, and M D Norris, and M Haber
Children's Leukaemia and Cancer Research Centre, Prince of Wales Children's Hospital, Randwick, Sydney, New South Wales, Australia.

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.

UI MeSH Term Description Entries
D008562 Membrane Glycoproteins Glycoproteins found on the membrane or surface of cells. Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001692 Biological Transport The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments. Transport, Biological,Biologic Transport,Transport, Biologic
D013752 Tetracycline A naphthacene antibiotic that inhibits AMINO ACYL TRNA binding during protein synthesis. 4-Epitetracycline,Achromycin,Achromycin V,Hostacyclin,Sustamycin,Tetrabid,Tetracycline Hydrochloride,Tetracycline Monohydrochloride,Topicycline,4 Epitetracycline
D013753 Tetracycline Resistance Nonsusceptibility of bacteria to the action of TETRACYCLINE which inhibits aminoacyl-tRNA binding to the 30S ribosomal subunit during protein synthesis.
D014407 Tumor Cells, Cultured Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely. Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D014700 Verapamil A calcium channel blocker that is a class IV anti-arrhythmia agent. Iproveratril,Calan,Cordilox,Dexverapamil,Falicard,Finoptin,Isoptin,Isoptine,Izoptin,Lekoptin,Verapamil Hydrochloride,Hydrochloride, Verapamil

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