title: Tumor cell culture survival following glucose and glutamine deprivation at typical physiological concentrations.
abstract: OBJECTIVE
  Most glucose (and glutamine)-deprivation studies of cancer cell cultures focus on total depletion, and are conducted over at least 24 h. It is difficult to extrapolate findings from such experiments to practical anti-glycolytic treatments, such as with insulin-inhibiting diets (with 10%-50% carbohydrate dietary restriction) or with isolated limb perfusion therapy (which usually lasts about 90 min). The aim of this study was to obtain experimental data on the effect of partial deprivation of d-glucose and l-glutamine (to typical physiological concentrations) during 0 to 6-h exposures of HeLa cells.
  
  
  METHODS
  HeLa cells were treated for 0 to 6 h with 6 mM d-glucose and 1 mM l-glutamine (normal in vivo conditions), 3 mM d-glucose and 0.5 mM l-glutamine (severe hypoglycemic conditions), and 0 mM d-glucose and 0 mM l-glutamine ("starvation"). Polarization-optical differential interference contrast and phase-contrast light microscopy were employed to investigate morphologic changes.
  
  
  RESULTS
  Reduction of glucose levels from 6 to 3 mM (and glutamine levels from 1 to 0.5 mM) brings about cancer cell survival of 73% after 2-h exposure and 63% after 4-h exposure. Reducing glucose levels from 6 to 0 mM (and glutamine levels from 1 to 0 mM) for 4 h resulted in 53% cell survival.
  
  
  CONCLUSIONS
  These data reveal that glucose (and glutamine) deprivation to typical physiological concentrations result in significant cancer cell killing after as little as 2 h. This supports the possibility of combining anti-glycolytic treatment, such as a carbohydrate-restricted diet, with chemotherapeutics for enhanced cancer cell killing.
authors.affiliation: Centre for Research and Continued Engineering Development, North-West University, Lynnwood Ridge, South Africa.
authors.forename: Edward Henry
authors.initials: EH
authors.lastname: Mathews
authors.affiliation: Department of Physiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
authors.forename: B André
authors.initials: BA
authors.lastname: Stander
authors.affiliation: Department of Physiology, School of Medicine, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
authors.forename: Annie M
authors.initials: AM
authors.lastname: Joubert
authors.affiliation: Centre for Research and Continued Engineering Development, North-West University, Lynnwood Ridge, South Africa. Electronic address: LLiebenberg@researchtoolbox.com.
authors.forename: Leon
authors.initials: L
authors.lastname: Liebenberg
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media / Q000737:chemistry; D005947:Glucose / Q000494:pharmacology* / Q000502:physiology; D005973:Glutamine / Q000494:pharmacology* / Q000502:physiology; D006019:Glycolysis; D006367:HeLa Cells; D006801:Humans; D007328:Insulin / Q000097:blood
chemical_list: D003470:Culture Media; D007328:Insulin; D005973:Glutamine; D005947:Glucose
keywords: Glucose deprivation; HeLa cell survival and morphology; Metabolic cancer control