Cancer cells switch from mitochondrial oxidative phosphorylation to glycolysis, even in the presence of normal
oxygen concentrations. Inhibition of the glycolytic pathway is therefore a critical strategy in
cancer therapy. A non-metabolic
glucose analog,
2-deoxy-D-glucose (2-DG), has been the focus of research on glycolytic inhibitors for use in
cancer treatment. The current study examined the anti-
cancer effects of 2-DG on
idarubicin (IDA)-resistant P388 (P388/IDA)
leukemia cells. P388/IDA cells were established following continuous exposure of IDA to P388 cells. Characterization of P388/IDA cells revealed increased
lactate production and
glucose consumption compared with P388 parent cells. The results of a cell viability assay determined that 2-DG induces higher toxicity in P388/IDA cells compared with P388 cells. Although 2-DG also exhibits endoplasmic reticulum (ER) stress-inducing activity, the cytotoxic effect of the ER stress inducer,
tunicamycin, on P388/IDA cells was lower than that of P388 cells. A combination of 2-DG and IDA enhanced P388/IDA cell death compared with each agent alone. The results indicated that P388 cells activated glycolysis after acquiring IDA resistance and therefore, inhibition of the glycolytic pathway via 2-DG might be a useful strategy for
cancer therapy against IDA- resistant
leukemia cells.