Tumor cell proliferation requires both growth signals and sufficient cellular bioenergetics. The AMP-activated protein kinase (AMPK) pathway seems dominant over the oncogenic signaling pathway suppressing cell proliferation. This study investigated the preclinical efficacy of targeting the tumor bioenergetic pathway using a glycolysis inhibitor 2-deoxyglucose (2DG) and AMPK agonists, AICAR and ...

Metabolic change in cancer cells by preferential production of energy through glycolysis is a well-documented characteristic of cancer. However, whether inhibition of glycolysis will enhance the efficacy of radiation therapy is a matter of debate. In this study which uses lung cancer as the model, we demonstrate that the improvement of radiotherapy by 2-deoxy-D-glucose (2DG) is p53-dependent. B...

Exposure to ionizing radiation is believed to cause cell injury via the production of free radicals that are thought to induce oxidative damage. It has been proposed that exposure to agents that enhance oxidative stressinduced injury by disrupting thiol metabolism may sensitize cells to the cytotoxic effects of ionizing radiation. Recently, it has been shown that glucose deprivation selectively...

      EGFR is a key molecule in cancer cells. EGFR signaling was shown to promote tumor cell proliferation and survival, invasion and angiogenesis and mediate resistance to treatment, including ionizing radiation in preclinical models. We extracted proteins from astrocytoma (III and IV) oligodendroglioma(IV) tumors and normal brain tissues and then evaluated the protein purity by Bradford test ...

PURPOSE The efficacy of solid tumor radioimmunotherapy is reduced by heterogeneous tumor distribution of the radionuclide, with dose mainly deposited in the normoxic region and by the relative radioresistance of hypoxic tumor cells. In an attempt to overcome these challenges, radioimmunotherapy was combined with 2-deoxy-d-glucose (2DG), a hypoxia-selective cytotoxic inhibitor of glucose metabol...

Nonmetabolizable glucose analogs inhibit the growth of Escherichia coli on a wide variety of carbon sources. This phenomenon was investigated with particular reference to the effect of 2-deoxyglucose (2DG) on growth on fructose as sole carbon source. When the inhibitor is supplied in sufficiently low concentrations, the initial arrest of growth is overcome; this relief of inhibition is aided by...

Hypoglycemia and neuroglucopenia stimulate AMP-activated protein kinase (AMPK) activity in the hypothalamus and this plays an important role in the counterregulatory responses, i.e. increased food intake and secretion of glucagon, corticosterone and catecholamines. Several upstream kinases that activate AMPK have been identified including Ca(2+)/Calmodulin-dependent protein kinase kinase (CaMKK...

Glucose deprivation has been hypothesized to cause cytotoxicity by inducing metabolic oxidative stress in human cancer cells. The current work tests the hypothesis that 2-deoxy-d-glucose (2DG) combined with cisplatin [cis-diamminedichloroplatinum(II)] can enhance cytotoxicity in human head and neck cancer cells (FaDu) by mechanisms involving oxidative stress. Exposure of FaDu cells to the combi...

Legionella pneumophila can grow intracellularly in A/J mouse macrophages. 2-Deoxy-D-glucose (2dG) (0.1, 1, and 10 mM) inhibited intracellular multiplication and promoted intracellular killing of L. pneumophila dose dependently when it was added to the culture medium of macrophage monolayers, whereas it did not inhibit the bacterial growth in buffered yeast extract broth, which was used for an L...

2-Deoxy-D-glucose (2DG), a glucose analog that transiently inhibits glycolysis, has anticonvulsant and antiepileptic disease-modifying properties in experimental in vivo models of seizures and epilepsy. Here we evaluated the effects of 2DG across the range of doses (50-500mg/kg i.p.) shown previously to exert anticonvulsant and antiepileptic effects in rats, on spatial learning and memory using...