2-Deoxy-D-glucose targeting of glucose metabolism in cancer cells as a potential therapy

Cancer cells are characterized by altered glucose metabolism known as the Warburg effect in which aerobic glycolysis is increased. Glucose is converted to lactate even under sufficient oxygen tension. Interfering with this process may be a potential effective strategy to cause cancer cell death because these cells rely heavily on glucose metabolism for survival and proliferation. 2-Deoxy-D-glucose (2DG), a glucose analog, targets glucose metabolism to deplete cancer cells of energy. In addition, 2DG increases oxidative stress, inhibits N-linked glycosylation, and induces autophagy. It can efficiently slow cell growth and potently facilitate apoptosis in specific cancer cells. Although 2DG itself has limited therapeutic effect in many types of cancers, it may be combined with other therapeutic agents or radiotherapy to exhibit a synergistic anticancer effect. In this review, we describe the Warburg effect and discuss 2DG and its underlying mechanisms and potential application for cancer treatment.