2-Deoxy-D-glucose enhances the anti-cancer effects of idarubicin on idarubicin-resistant P388 leukemia cells

Abstract

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 IDAresistant leukemia cells.