title: Chronic Dietary Administration of the Glycolytic Inhibitor 2-Deoxy-D-Glucose (2-DG) Inhibits the Growth of Implanted Ehrlich's Ascites Tumor in Mice.
abstract: BACKGROUND
  Dietary energy restriction (DER) has been well established as a potent anticancer strategy. Non-adoption of restricted diet for an extended period has limited its practical implementation in humans with a compelling need to develop agents that mimic effects similar to DER, without reduction in actual dietary intake. Glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), has recently been shown to possess potential as an energy restriction mimetic agent (ERMA). In the present study we evaluated the effect of dietary 2-DG administration on a mouse tumor model, with a focus on several potential mechanisms that may account for the inhibition of tumorigenesis.
  
  
  RESULTS
  Swiss albino strain 'A' mice were administered with 0.2% and 0.4% w/v 2-DG in drinking water for 3 months prior to tumor implantation (Ehrlich's ascites carcinoma; EAC) and continued till the termination of the study with no adverse effects on general physiology and animal growth. Dietary 2-DG significantly reduced the tumor incidence, delayed the onset, and compromised the tumor growth along with enhanced survival. We observed reduced blood glucose and serum insulin levels along with decreased proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine positive (BrdU+) tumor cells in 2-DG fed mice. Also, reduced levels of certain key players of metabolic pathways such as phosphatidylinositol 3-kinase (PI3K), phosphorylated-Akt and hypoxia inducible factor-1 alpha (HIF-1α) were also noted in tumors of 2-DG fed mice. Further, decrease in CD4+/CD8+ ratio and T-regulatory cells observed in 2-DG fed mice suggested enhanced antitumor immunity and T cell effector function.
  
  
  CONCLUSIONS
  These results strongly suggest that dietary 2-DG administration in mice, at doses easily achievable in humans, suitably modulates several pleotrophic factors mimicking DER and inhibits tumorigenesis, emphasizing the use of ERMAs as a promising cancer preventive strategy.
authors.affiliation: Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. SK Mazumdar Road, Delhi, India; Medical Biotechnology Laboratory, Dr B.R Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Singh
authors.affiliation: Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. SK Mazumdar Road, Delhi, India; Medical Biotechnology Laboratory, Dr B.R Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Pandey
authors.affiliation: Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. SK Mazumdar Road, Delhi, India.
authors.forename: Anant Narayan
authors.initials: AN
authors.lastname: Bhatt
authors.affiliation: Medical Biotechnology Laboratory, Dr B.R Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India.
authors.forename: Richa
authors.initials: R
authors.lastname: Chaudhary
authors.affiliation: Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. SK Mazumdar Road, Delhi, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Bhuria
authors.affiliation: Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. SK Mazumdar Road, Delhi, India.
authors.forename: Namita
authors.initials: N
authors.lastname: Kalra
authors.affiliation: Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. SK Mazumdar Road, Delhi, India.
authors.forename: Ravi
authors.initials: R
authors.lastname: Soni
authors.affiliation: Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. SK Mazumdar Road, Delhi, India.
authors.forename: Bal Gangadhar
authors.initials: BG
authors.lastname: Roy
authors.affiliation: Medical Biotechnology Laboratory, Dr B.R Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India.
authors.forename: Daman
authors.initials: D
authors.lastname: Saluja
authors.affiliation: Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Brig. SK Mazumdar Road, Delhi, India.
authors.forename: Bilikere S
authors.initials: BS
authors.lastname: Dwarakanath
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D016516:CD4-CD8 Ratio; D031204:Caloric Restriction; D002286:Carcinoma, Ehrlich Tumor / Q000098:blood supply / Q000188:drug therapy* / Q000276:immunology; D002455:Cell Division / Q000187:drug effects; D003847:Deoxyglucose / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006019:Glycolysis / Q000187:drug effects*; D007328:Insulin / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D051379:Mice; D009363:Neoplasm Proteins / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011292:Premedication; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000964:Antimetabolites, Antineoplastic; D001786:Blood Glucose; D007328:Insulin; D009363:Neoplasm Proteins; D003847:Deoxyglucose; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse