Tumor cell culture survival following glucose and glutamine deprivation at typical physiological concentrations

Edward Henry Mathews, B. André Stander, Annie M. Joubert, Leon Liebenberg

Research output: Contribution to journalArticlepeer-review

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 invivo 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)218-227
Number of pages10
JournalNutrition
Volume30
Issue number2
DOIs
StatePublished - Feb 2014
Externally publishedYes

Keywords

  • Glucose deprivation
  • HeLa cell survival and morphology
  • Metabolic cancer control

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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