The human KB multidrug-resistant cell line KB-C1 is hypersensitive to inhibitors of glycosylation.
We have previously shown that the hypersensitivity of KB MDR cells to 2-deoxy-D-glucose is associated with diminished plasma membrane GLUT-1 levels compared with parental, non-MDR cells. Here we report that MDR cells are hypersensitive to the N-linked glycosylation inhibitor tunicamycin, which induces partial inhibition of GLUT-1 glycosylation and diminishes GLUT-1-mediated transport. The effect of tunicamycin, which also enhances the hypersensitivity of MDR cells to 2-deoxy-D-glucose, could not be attributed to alterations in P-glycoprotein activity. The use of agents that act synergistically to diminish the level and activity of GLUT-1 in MDR cells may be of clinical potential.
Bentley
J
J
Department of Biology, The University of York, UK.
Quinn
D M
DM
Pitman
R S
RS
Warr
J R
JR
Kellett
G L
GL
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D003847:Deoxyglucose / Q000494:pharmacology; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000378:metabolism*; D018432:Drug Resistance, Multiple / Q000502:physiology*; D019008:Drug Resistance, Neoplasm; D005947:Glucose / Q000493:pharmacokinetics; D051272:Glucose Transporter Type 1; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D007624:KB Cells / Q000187:drug effects* / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000900:Anti-Bacterial Agents; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495677:SLC2A1 protein, human; D014415:Tunicamycin; D003847:Deoxyglucose; D005947:Glucose