Glucose, not glutamine, is the dominant energy source required for proliferation and survival of head and neck squamous carcinoma cells

Vlad C. Sandulache, Thomas J. Ow, Curtis R. Pickering, Mitchell J. Frederick, Ge Zhou, Izabela Fokt, Melinda Davis-Malesevich, Waldemar Priebe, Jeffrey N. Myers

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

BACKGROUND: Tumor metabolism is an essential contributor to disease progression and response to treatment. An understanding of the metabolic phenotype of head and neck squamous cell carcinoma (HNSCC) will allow the development of appropriate antimetabolic strategies for this tumor type. METHODS: A panel of 15 HNSCC cell lines was assayed for glucose and glutamine dependence and sensitivity to metabolic inhibitors. In addition, broad-spectrum metabolomic analysis using mass spectrometry/liquid chromatography was combined with individual measurements of reducing potential, adenosine triphosphate, and lactate production to characterize cellular metabolic phenotypes. RESULTS: HNSCC energy and reducing potential levels closely mirrored extracellular glucose concentrations. Glucose starvation induced cell death despite the activation of secondary energetic pathways. Conversely, glutamine was not required for HNSCC survival and did not serve as a significant source of energy. 2-deoxyglucose (2-DG) and its fluorinated derivative decreased glycolytic and Krebs cycle activity, cellular energy, and reducing potential and inhibited HNSCC cell proliferation. 2-DG effects were potentiated by the addition of metformin, but not by inhibitors of the pentose phosphate pathway or glutaminolysis. Despite dependence on glucose catabolism, the authors identified a subset of cell lines with relative resistance to starvation. Exploration of 1 such cell line (HN30) suggested that the presence of wild-type p53 can partially protect tumor cells from glucose starvation. CONCLUSIONS: HNSCC tumor cells are dependent on glucose, not glutamine, for energy production and survival, providing a rationale for treatment strategies that target glucose catabolism. However, antimetabolic strategies may need to be tailored to the tumor background, more specifically, p53 status.

Original languageEnglish (US)
Pages (from-to)2926-2938
Number of pages13
JournalCancer
Volume117
Issue number13
DOIs
StatePublished - Jul 1 2011
Externally publishedYes

Fingerprint

Glutamine
Glucose
Starvation
Deoxyglucose
Neoplasms
Cell Line
Phenotype
Pentose Phosphate Pathway
Metabolomics
Citric Acid Cycle
Metformin
Carcinoma, squamous cell of head and neck
Liquid Chromatography
Disease Progression
Lactic Acid
Mass Spectrometry
Spectrum Analysis
Cell Survival
Cell Death
Adenosine Triphosphate

Keywords

  • 2-deoxyglucose
  • glutamine
  • glycolysis
  • metabolism
  • reducing potential

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Sandulache, V. C., Ow, T. J., Pickering, C. R., Frederick, M. J., Zhou, G., Fokt, I., ... Myers, J. N. (2011). Glucose, not glutamine, is the dominant energy source required for proliferation and survival of head and neck squamous carcinoma cells. Cancer, 117(13), 2926-2938. https://doi.org/10.1002/cncr.25868

Glucose, not glutamine, is the dominant energy source required for proliferation and survival of head and neck squamous carcinoma cells. / Sandulache, Vlad C.; Ow, Thomas J.; Pickering, Curtis R.; Frederick, Mitchell J.; Zhou, Ge; Fokt, Izabela; Davis-Malesevich, Melinda; Priebe, Waldemar; Myers, Jeffrey N.

In: Cancer, Vol. 117, No. 13, 01.07.2011, p. 2926-2938.

Research output: Contribution to journalArticle

Sandulache, VC, Ow, TJ, Pickering, CR, Frederick, MJ, Zhou, G, Fokt, I, Davis-Malesevich, M, Priebe, W & Myers, JN 2011, 'Glucose, not glutamine, is the dominant energy source required for proliferation and survival of head and neck squamous carcinoma cells', Cancer, vol. 117, no. 13, pp. 2926-2938. https://doi.org/10.1002/cncr.25868
Sandulache, Vlad C. ; Ow, Thomas J. ; Pickering, Curtis R. ; Frederick, Mitchell J. ; Zhou, Ge ; Fokt, Izabela ; Davis-Malesevich, Melinda ; Priebe, Waldemar ; Myers, Jeffrey N. / Glucose, not glutamine, is the dominant energy source required for proliferation and survival of head and neck squamous carcinoma cells. In: Cancer. 2011 ; Vol. 117, No. 13. pp. 2926-2938.
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AU - Ow, Thomas J.

AU - Pickering, Curtis R.

AU - Frederick, Mitchell J.

AU - Zhou, Ge

AU - Fokt, Izabela

AU - Davis-Malesevich, Melinda

AU - Priebe, Waldemar

AU - Myers, Jeffrey N.

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N2 - BACKGROUND: Tumor metabolism is an essential contributor to disease progression and response to treatment. An understanding of the metabolic phenotype of head and neck squamous cell carcinoma (HNSCC) will allow the development of appropriate antimetabolic strategies for this tumor type. METHODS: A panel of 15 HNSCC cell lines was assayed for glucose and glutamine dependence and sensitivity to metabolic inhibitors. In addition, broad-spectrum metabolomic analysis using mass spectrometry/liquid chromatography was combined with individual measurements of reducing potential, adenosine triphosphate, and lactate production to characterize cellular metabolic phenotypes. RESULTS: HNSCC energy and reducing potential levels closely mirrored extracellular glucose concentrations. Glucose starvation induced cell death despite the activation of secondary energetic pathways. Conversely, glutamine was not required for HNSCC survival and did not serve as a significant source of energy. 2-deoxyglucose (2-DG) and its fluorinated derivative decreased glycolytic and Krebs cycle activity, cellular energy, and reducing potential and inhibited HNSCC cell proliferation. 2-DG effects were potentiated by the addition of metformin, but not by inhibitors of the pentose phosphate pathway or glutaminolysis. Despite dependence on glucose catabolism, the authors identified a subset of cell lines with relative resistance to starvation. Exploration of 1 such cell line (HN30) suggested that the presence of wild-type p53 can partially protect tumor cells from glucose starvation. CONCLUSIONS: HNSCC tumor cells are dependent on glucose, not glutamine, for energy production and survival, providing a rationale for treatment strategies that target glucose catabolism. However, antimetabolic strategies may need to be tailored to the tumor background, more specifically, p53 status.

AB - BACKGROUND: Tumor metabolism is an essential contributor to disease progression and response to treatment. An understanding of the metabolic phenotype of head and neck squamous cell carcinoma (HNSCC) will allow the development of appropriate antimetabolic strategies for this tumor type. METHODS: A panel of 15 HNSCC cell lines was assayed for glucose and glutamine dependence and sensitivity to metabolic inhibitors. In addition, broad-spectrum metabolomic analysis using mass spectrometry/liquid chromatography was combined with individual measurements of reducing potential, adenosine triphosphate, and lactate production to characterize cellular metabolic phenotypes. RESULTS: HNSCC energy and reducing potential levels closely mirrored extracellular glucose concentrations. Glucose starvation induced cell death despite the activation of secondary energetic pathways. Conversely, glutamine was not required for HNSCC survival and did not serve as a significant source of energy. 2-deoxyglucose (2-DG) and its fluorinated derivative decreased glycolytic and Krebs cycle activity, cellular energy, and reducing potential and inhibited HNSCC cell proliferation. 2-DG effects were potentiated by the addition of metformin, but not by inhibitors of the pentose phosphate pathway or glutaminolysis. Despite dependence on glucose catabolism, the authors identified a subset of cell lines with relative resistance to starvation. Exploration of 1 such cell line (HN30) suggested that the presence of wild-type p53 can partially protect tumor cells from glucose starvation. CONCLUSIONS: HNSCC tumor cells are dependent on glucose, not glutamine, for energy production and survival, providing a rationale for treatment strategies that target glucose catabolism. However, antimetabolic strategies may need to be tailored to the tumor background, more specifically, p53 status.

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