Potentiation by 2-deoxy-D-glucose tetraacetate of the cytostatic action of alpha-difluoromethylornithine in tumoral insulin-producing cells.
Insulin-producing tumoral cells of the RINm5F line were cultured for 8 to 96 h in the absence or presence of 2-deoxy-D-glucose tetraacetate (0.01 mM to 1.0 mM) and/or á-difluoromethylornithine (also 0.01 mM to 1.0 mM). The ester of the glucose analog potentiated the inhibitory action of the ornithine decarboxylase inhibitor. For instance, when both agents were tested in combination at a concentration of 0.01 mM each, the generation of formazan from 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium was decreased, within 2 days, to 23.2+/- 6.1% of its paired control value, whilst neither the ester of 2-deoxy-D-glucose nor the ornithine analog exerted any significant effect upon cell growth when used separately at the same low concentration and over the same length of culture. These findings suggest that 2-deoxy-D-glucose tetraacetate could be used to sensitize tumoral cells to the cytostatic action of established chemotherapeutic agents in the treatment of neoplastic diseases.
Laboratory of Experimental Medicine, Brussels Free University, B-1070 Brussels, Belgium.
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E
Olivares
W J
WJ
Malaisse
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D000518:Eflornithine / Q000633:toxicity*; D005947:Glucose / Q000633:toxicity*; D007340:Insulinoma; D007700:Kinetics; D065108:Ornithine Decarboxylase Inhibitors; D010190:Pancreatic Neoplasms; D014407:Tumor Cells, Cultured
C115456:2-deoxy-glucose tetraacetate; D000970:Antineoplastic Agents; D065108:Ornithine Decarboxylase Inhibitors; D005947:Glucose; D000518:Eflornithine