2. Academic Validation
  3. Glutamine Modulates Expression and Function of Glucose 6-Phosphate Dehydrogenase via NRF2 in Colon Cancer Cells

Glutamine Modulates Expression and Function of Glucose 6-Phosphate Dehydrogenase via NRF2 in Colon Cancer Cells

  • Antioxidants (Basel). 2021 Aug 25;10(9):1349. doi: 10.3390/antiox10091349.
Ibrahim H Polat 1 2 3,  Míriam Tarrado-Castellarnau 1 2 4,  Adrian Benito 1 2,  Claudia Hernandez-Carro 1 2,  Josep Centelles 1 2 4,  Silvia Marin 1 2 4,  Marta Cascante 1 2 4
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, Universitat de Barcelona, Av Diagonal 643, 08028 Barcelona, Spain.
  • 2 Institute of Biomedicine, Universitat de Barcelona (IBUB), 08028 Barcelona, Spain.
  • 3 Equipe Environnement et Prédiction de la Santé des Populations, Laboratoire TIMC (UMR 5525), CHU de Grenoble, Université Grenoble Alpes, CEDEX, 38700 La Tronche, France.
  • 4 CIBER of Hepatic and Digestive Diseases (CIBEREHD), Institute of Health Carlos III (ISCIII), 28029 Madrid, Spain.
PMID: 34572981 DOI: 10.3390/antiox10091349
Abstract

Nucleotide pools need to be constantly replenished in Cancer cells to support cell proliferation. The synthesis of nucleotides requires glutamine and 5-phosphoribosyl-1-pyrophosphate produced from ribose-5-phosphate via the oxidative branch of the pentose phosphate pathway (ox-PPP). Both PPP and glutamine also play a key role in maintaining the redox status of Cancer cells. Enhanced glutamine metabolism and increased glucose 6-phosphate dehydrogenase (G6PD) expression have been related to a malignant phenotype in tumors. However, the association between G6PD overexpression and glutamine consumption in Cancer cell proliferation is still incompletely understood. In this study, we demonstrated that both inhibition of G6PD and glutamine deprivation decrease the proliferation of colon Cancer cells and induce cell cycle arrest and Apoptosis. Moreover, we unveiled that glutamine deprivation induce an increase of G6PD expression that is mediated through the activation of the nuclear factor (erythroid-derived 2)-like 2 (NRF2). This crosstalk between G6PD and glutamine points out the potential of combined therapies targeting oxidative PPP Enzymes and glutamine catabolism to combat colon Cancer.

Keywords

cancer cell metabolism; colon cancer; glucose-6-phosphate dehydrogenase; oxidative stress; pentose phosphate pathway.

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