Abstract:
The inhibitor in glycolysis, 2-deoxyglucose (2-DG), proved to have a definite inhibition towards many types of cancer cells. As a candidate anti-tumor drug, 2-DG has been studied for nearly half a century. Over the past few years, a series of studies have shown that more sophisticated mechanisms of 2-DG against cancer cells may exist, which was previously not given, sufficient attention. Aside from its typical mechanism of inhibiting glycolysis, 2-DG also can interfere with glycosylation by disturbing the formation of oligosaccharides. This action induces unfolded protein response in the endoplasmic reticulum and in active cell apoptosis. 2-DG can also increase the specific glycosylation of proteins from several genes to suppress the correlated transcription factors and interfere with the growth of cancer cells. When used alone, 2-DG can directly activate apoptosis via several intracellular signal pathways and release some factors to suppress the growth of tumor cells in vitro. 2-DG can inhibit cancer cells by interfering with intracellular redox and maintaining intracellular redox stress to induce the apoptosis of cancer cells. When combined with other treatments, 2-DG can be sensitive to radiotherapy and chemotherapy with a limited effect that is formerly attributed to the resistance of cells to therapies. Moreover, 2-DG can protect normal cells from damage by chemotherapy. Animal experiments proved that 2-DG also inhibits xenograft tumor cells in rats. Several institutes abroad are engaged in Phase-I clinical studies. The results of their studies indicated that 2-DG has a relatively low toxicity and a short half-life in the human body. However, in Mainland China, little attention has been given on the subject. In this summary, we perform a straightforward review of the mechanisms of the inhibitory action against tumor cells that have been proven in the last few years and focus on other mechanisms aside from the typical inhibition effects of glycolysis.