Glutamine modulates expression and function of glucose 6-phosphate dehydrogenase via NRF2 in colon cancer cells
| Autor: | Míriam Tarrado-Castellarnau, Silvia Marin, Claudia Hernandez-Carro, Marta Cascante, Adrian Benito, Ibrahim H. Polat, Josep J. Centelles |
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| Rok vydání: | 2021 |
| Předmět: |
Glutamina
Cancer cells Physiology Colon Glutamine Clinical Biochemistry pentose phosphate pathway RM1-950 Oxidative phosphorylation Pentose phosphate pathway cancer cell metabolism Biochemistry Article chemistry.chemical_compound ddc:570 Glucose-6-phosphate dehydrogenase oxidative stress Nucleotide ddc:610 Molecular Biology chemistry.chemical_classification Cell growth Cell Biology Cell biology Glucose chemistry colon cancer Apoptosis Cancer cell glucose-6-phosphate dehydrogenase Glucosa Cèl·lules canceroses Therapeutics. Pharmacology Còlon |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Antioxidants Volume 10 Issue 9 Antioxidants, Vol 10, Iss 1349, p 1349 (2021) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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