title: Differential cytotoxicity of the glycolytic inhibitor 2-deoxy-D-glucose in isogenic cell lines varying in their p53 status.
abstract: BACKGROUND
  Earlier studies have shown that cytotoxicity of glycolic inhibitor 2-deoxy-D-glucose is heterogeneous among different tumor cell lines due to a number of reasons including difference in p53 status.
  
  
  OBJECTIVE
  To investigate the cytotoxic effects of 2-DG in isogenic cell systems that differ in their p53 status.
  
  
  METHODS
  Head and neck carcinoma cells KB and its two p53 mutants (KB68-mutation in transactivation domain (Arg/Cys) at position 68 and KB110-mutation in proline rich deoxyribonucleic acid binding domain (Glu/Gly) at position 110) were used as the model. Clonogenecity, cell proliferation, cell cycle, annexin V assay, intracellular levels of ROS and NADP+/NADPH levels were investigated as parameters for 2-DG induced cytotoxicity.
  
  
  RESULTS
  Macrocolony assay showed that the cytotoxicity of 2-DG was time- and concentration-dependent. However, the sensitivity of the three cell lines were quantitatively different, with KB110 being more sensitive than the parental cell line KB and KB68. The effects of 2-DG on growth inhibition, cell cycle, and apoptosis correlated well with the changes in cell survival in these cells. A higher degree of 2-DG induced enhancement in the metabolic oxidative stress was evident in both the mutant cell lines (elevated ROS level and NADP+/NADPH ratio) suggestive of a higher degree of compromize in the antioxidant defense in the mutant cells.
  
  
  CONCLUSIONS
  2-DG could be considered as a potential therapeutic agent that induces cell death (which could be linked to induced oxidative stress) selectively in tumors with p53 mutations (particularly in the proline rich region).
authors: Archana
authors: A
authors: Vibhuti
authors: Kambadur
authors: K
authors: Muralidhar
authors: Division of Radiation Biosciences, Institute of Nuclear Medicine And Allied Sciences, Delhi, India.
authors: Bilikere S
authors: BS
authors: Dwarakanath
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D000963:Antimetabolites / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003847:Deoxyglucose / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D009249:NADP / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D017382:Reactive Oxygen Species; D000077195:Squamous Cell Carcinoma of Head and Neck; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D017304:Annexin A5; D000963:Antimetabolites; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D009249:NADP; D003847:Deoxyglucose