2-Deoxy-D-glucose

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Background

2-Deoxy-D-glucose (2DG), glucose analogue, is a competitive glycolytic inhibitor [1] [2] [3]. Cytotoxicity assays displayed IC50 values of 2DG in KIT-positive GIST cell lines between 0.5μM (GIST882 cell line) and 2.5μM (GIST430 cell line) [4]. Glycolysis is an ATP-producing subsystem [5].If the physiologically relevant ratio of 2DG/glucose is 0.8, the glucose metabolism in the FaDu cells that are growing in DMEM containing 25 mmol/L glucose will be inhibited. Treatment with 2DG caused a 30% to 40% decrease in total glutathione content and 32% cell killing relative to untreated control cells [2]. 2-DG inhibited PEDV propagation in a concentration-dependent manner and induced endoplasmic reticulum stress in Vero cells. The 2-DG treatment did not significantly affect virus entry. But further research showed that 2-DG decreased viral protein translation, implying that 2-DG might affect virus replication at the early stage of virus infection. Additionally, the 2-DG treatment increased the expression level of CD13 [6]. 2-Deoxy-D-glucose increases the efficacy of adriamycin and paclitaxel in human osteosarcoma and non-small cell lung cancers in vivo in retarding tumor growth and prolonging survival [3]. In Sparus aurata L., 2-DG increased blood glucose levels in a statistically significant way, caused a non-statistically significant decrease in the respiratory burst activity of head kidney leucocytes. Peroxidase activity measured in serum and head kidney leukocyte showed no statistically significant difference with respect to the control values [7].

[1]. John Laszlo, William R. Harlan, Robert F. Klein, et al. The Effect of 2-Deoxy-D-Glucose Infusions on Lipid and Carbohydrate Metabolism in Man. J Clin Invest., 1961, 40(1):171-176.
[2]. Andrean L. Simons, Iman M. Ahmad, David M. Mattson, et al. 2-Deoxy-D-Glucose Combined with Cisplatin Enhances Cytotoxicity via Metabolic Oxidative Stress in Human Head and NeckCancer Cells. Cancer Research, 2007, 67(7): 3364-3371.
[3]. Gregory Maschek, Niramol Savaraj, Waldemar Priebe, et al. 2-Deoxy-D-glucose Increases the Efficacy of Adriamycin and Paclitaxel in Human Osteosarcoma and Non-Small Cell Lung Cancers In Vivo. Cancer Research, 2004, 64:31-34.
[4]. Thomas Mühlenberg, Susanne Grunewald, Jürgen Treckmann, et al. Inhibition of KIT-Glycosylation by 2-Deoxyglucose Abrogates KIT-Signaling and Combination with ABT-263 Synergistically Induces Apoptosis in Gastrointestinal Stromal Tumor. PLOS ONE, 2015, 10(3):e0120531.
[5]. R. J. Connett, C. R. Honig, T. E. Gayeski, et al. Defining hypoxia: a systems view of VO2, glycolysis, energetics, and intracellular PO2. Journal of Applied Physiology, 1990, 68(3): 833-842.
[6]. Yue Wang, Jia-rong Li, Ming-xia Sun, et al. Triggering unfolded protein response by 2-Deoxy-D-glucose inhibits porcine epidemic diarrhea virus propagation. Antiviral Research, 2014, 106: 33–41.
[7]. F.A. Guardiola, R. Cerezuela, J. Meseguer, et al. Effects of 2-deoxy-D-glucose on the immune system of seabream (Sparus aurata L.). Fish & Shellfish Immunology, 2011, 30: 592-599.