{"title":"Gene Expression of Glycolysis Enzymes in MCF-7 Breast Cancer Cells Exposed to Warburg Effect and Hypoxia.","authors":"Irem Bayar, Gamze Sevri Ekren Asici, Ayşegül Bildik, Funda Kiral","doi":"10.22088/IJMCM.BUMS.13.1.29","DOIUrl":null,"url":null,"abstract":"<p><p>Hypoxia can cause significant changes in the glucose metabolism of cancer cells that prefer aerobic glycolysis for energy production instead of the conventional oxidative phosphorylation mechanism. In this study, breast cancer cells (MCF-7) were exposed to glucose (0-5.5-15-55 mM), during specific incubation periods (3, 6, 12, or 24 hours) under normoxic and hypoxic conditions. The expression levels of hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1), and glycolytic enzymes at varying glucose concentrations in cells were investigated in the different oxygen environments. It was determined that glycolytic enzymes [Hexokinase 2 (HK2), Pyruvate Kinase M2 (PKM2), Glucose-6-phosphate dehydrogenase (G6PD), Lactate Dehydrogenase A (LDHA), Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH), and Phosphofructokinase M (PFKM)] increased at the transcriptional level, especially in the first hours. This increase indicates that major metabolic reprogramming in response to hypoxia probably occurs over a short period of time. The increase in G6PD gene expression under high glucose and hypoxia conditions suggests that the pentose phosphate pathway (PPP) is used by cancer cells to synthesize necessary precursors for the cell. The results of the study showed that there is a significant interaction between hypoxia and glycolytic metabolism in cancer cells. It is thought that metabolic pathways activated by hypoxia and related genes located in these pathways will contribute to the literature by offering the potential to be target molecules for therapeutic purposes.</p>","PeriodicalId":14152,"journal":{"name":"International Journal of Molecular and Cellular Medicine","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11329934/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Molecular and Cellular Medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.22088/IJMCM.BUMS.13.1.29","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Hypoxia can cause significant changes in the glucose metabolism of cancer cells that prefer aerobic glycolysis for energy production instead of the conventional oxidative phosphorylation mechanism. In this study, breast cancer cells (MCF-7) were exposed to glucose (0-5.5-15-55 mM), during specific incubation periods (3, 6, 12, or 24 hours) under normoxic and hypoxic conditions. The expression levels of hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1), and glycolytic enzymes at varying glucose concentrations in cells were investigated in the different oxygen environments. It was determined that glycolytic enzymes [Hexokinase 2 (HK2), Pyruvate Kinase M2 (PKM2), Glucose-6-phosphate dehydrogenase (G6PD), Lactate Dehydrogenase A (LDHA), Glyceraldehyde-3-phosphate Dehydrogenase (GAPDH), and Phosphofructokinase M (PFKM)] increased at the transcriptional level, especially in the first hours. This increase indicates that major metabolic reprogramming in response to hypoxia probably occurs over a short period of time. The increase in G6PD gene expression under high glucose and hypoxia conditions suggests that the pentose phosphate pathway (PPP) is used by cancer cells to synthesize necessary precursors for the cell. The results of the study showed that there is a significant interaction between hypoxia and glycolytic metabolism in cancer cells. It is thought that metabolic pathways activated by hypoxia and related genes located in these pathways will contribute to the literature by offering the potential to be target molecules for therapeutic purposes.
期刊介绍:
The International Journal of Molecular and Cellular Medicine (IJMCM) is a peer-reviewed, quarterly publication of Cellular and Molecular Biology Research Center (CMBRC), Babol University of Medical Sciences, Babol, Iran. The journal covers all cellular & molecular biology and medicine disciplines such as the genetic basis of disease, biomarker discovery in diagnosis and treatment, genomics and proteomics, bioinformatics, computer applications in human biology, stem cells and tissue engineering, medical biotechnology, nanomedicine, cellular processes related to growth, death and survival, clinical biochemistry, molecular & cellular immunology, molecular and cellular aspects of infectious disease and cancer research. IJMCM is a free access journal. All open access articles published in IJMCM are distributed under the terms of the Creative Commons Attribution CC BY. The journal doesn''t have any submission and article processing charges (APCs).