title: Metabolic response of glioblastoma cells associated with glucose withdrawal and pyruvate substitution as revealed by GC-MS.
abstract: BACKGROUND
  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. 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to mass spectrometry (GC-MS) to analyze how glioblastoma brain tumor cells respond metabolically when glucose is withdrawn and substituted by pyruvate.
  
  
  METHODS
  Glioblastoma 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  Our 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.
authors: Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Leipzig AöR, Liebigstraße 19, Leipzig, 04103 Germany.
authors: Henry
authors: 0000-0001-9216-5918
authors: H
authors: Oppermann
authors: Institut für Analytische Chemie, Fakultät für Chemie & Mineralogie der Universität Leipzig, Linnéstraße 3, Leipzig, 04103 Germany.
authors: Yonghong
authors: Y
authors: Ding
authors: Institut für Analytische Chemie, Fakultät für Chemie & Mineralogie der Universität Leipzig, Linnéstraße 3, Leipzig, 04103 Germany.
authors: Jeevan
authors: J
authors: Sharma
authors: Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Leipzig AöR, Liebigstraße 19, Leipzig, 04103 Germany.
authors: Mandy
authors: M
authors: Berndt Paetz
authors: Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Leipzig AöR, Liebigstraße 19, Leipzig, 04103 Germany.
authors: Jürgen
authors: J
authors: Meixensberger
authors: Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Leipzig AöR, Liebigstraße 19, Leipzig, 04103 Germany.
authors: Frank
authors: F
authors: Gaunitz
authors: Institut für Analytische Chemie, Fakultät für Chemie & Mineralogie der Universität Leipzig, Linnéstraße 3, Leipzig, 04103 Germany.
authors: Claudia
authors: C
authors: Birkemeyer
keywords: Cancer; Glioblastoma; Glucose; Metabolite profiling; Pyruvate; Warburg effect