Abstract
BackgroundTumor cells are highly dependent on glucose even in the presence of oxygen. This concept called the Warburg effect is a hallmark of cancer and strategies are considered to therapeutically exploit the phenomenon such as ketogenic diets. The success of such strategies is dependent on a profound understanding of tumor cell metabolism. With new techniques it is now possible to thoroughly analyze the metabolic responses to the withdrawal of substrates and their substitution by others. In the present study we used gas chromatography coupled to mass spectrometry (GC-MS) to analyze how glioblastoma brain tumor cells respond metabolically when glucose is withdrawn and substituted by pyruvate.MethodsGlioblastoma brain tumor cells were cultivated in medium with high (25 mM), medium (11 mM) or low (5.5 mM) glucose concentration or with pyruvate (5 mM). After 24 h GC-MS metabolite profiling was performed.ResultsThe abundances of most metabolites were dependent on the supply of glucose in tendency but not in a linear manner indicating saturation at high glucose. Noteworthy, a high level of sorbitol production and release was observed at high concentrations of glucose and high release of alanine, aspartate and citrate were observed when glucose was substituted by pyruvate. Intermediates of the TCA cycle were present under all nutritional conditions and evidence was found that cells may perform gluconeogenesis from pyruvate.ConclusionsOur experiments reveal a high plasticity of glioblastoma cells to changes in nutritional supply which has to be taken into account in clinical trials in which specific diets are considered for therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-016-0131-9) contains supplementary material, which is available to authorized users.
Highlights
Tumor cells are highly dependent on glucose even in the presence of oxygen
In the present work we used gas chromatography (GC) coupled to mass spectrometry (MS) to analyze the metabolic response of glioblastoma cells to the presence of different concentrations of glucose and in a situation when glucose is substituted by pyruvate
D-lactate, L-lactate and MGO production at different concentrations of glucose and supply of pyruvate In order to investigate how different concentrations of glucose in the medium contribute to the glycolytic flux in U87 glioblastoma cells, we determined the production of L-lactate in medium with different concentrations of glucose and in the presence of 5 mM pyruvate instead of glucose
Summary
Tumor cells are highly dependent on glucose even in the presence of oxygen. This concept called the Warburg effect is a hallmark of cancer and strategies are considered to therapeutically exploit the phenomenon such as ketogenic diets. The success of such strategies is dependent on a profound understanding of tumor cell metabolism. The most prominent feature of tumor cell metabolism is the so-called Warburg effect which describes a strong dependence on glycolytic production of ATP accompanied by the conversion of pyruvate to lactate even in the presence of oxygen (aerobic glycolysis).
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