Two-deoxyglucose as an anti-metabolite in human carcinoma cell line RPMI-2650 and drug-resistant variants.
The accumulation of 2-deoxyglucose (2-DG), a glycolytic inhibitor, was investigated in a human nasal carcinoma cell line, RPMI-2650 and two of its drug-resistant variants (selected with taxol and melphalan) to assess manipulation of glycolytic potential as a selective means of reducing resistance. 2-DG uptake was increased 3-fold and 9.9-fold in taxol- and melphalan-resistant variants of RPMI-2650, respectively. Two of the principal factors associated with increased 2-DG uptake, namely glucose transporters and hexokinase activity, were increased in the resistant variants. Other changes in glucose metabolism that may affect 2-DG as an antimetabolite were observed, including increases in glucose-6-phosphate dehydrogenase of 10-fold and 100-fold for taxol- and melphalan-resistant variants, respectively, suggesting higher pentose phosphate activity; increased glutamine utilisation and greater sensitivity to iodoacetic acid-induced depletion of ATP levels in the parent relative to the resistant variants.
Keenan
J
J
National Cell and Tissue Culture Centre/National Institute of Cellular Biology, Dublin City University, Glasnevin, Dublin 9, Ireland. joanne.keenan@dcu.ie
Liang
Y
Y
Clynes
M
M
D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D003847:Deoxyglucose / Q000493:pharmacokinetics / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005947:Glucose / Q000378:metabolism; D006801:Humans; D009300:Nasal Septum; D009669:Nose Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D014316:Tritium
D000964:Antimetabolites, Antineoplastic; D014316:Tritium; D003847:Deoxyglucose; D005947:Glucose