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Vol. 65 No. 7: Issue 7

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Glucose restriction reverses the Warburg effect and modulates PKM2 and mTOR expression in breast cancer cell lines

https://doi.org/10.14715/cmb/2019.65.7.6
Roula Tahtouh
Cancer and Metabolism Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon
Layal Wardi
Cancer and Metabolism Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon
Riad Sarkis
Faculty of Medicine, Saint-Joseph University and Hotel-Dieu de France, Surgery Department, Beirut, Lebanon
Ray Hachem
Department of Infectious Diseases, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Issam Raad
Department of Infectious Diseases, University of Texas MD Anderson Cancer Center, Houston, Texas, USA
Nabil El Zein
Life & Earth Sciences department, Faculty of Sciences, Lebanese University, Beirut, Lebanon
George Hilal
Cancer and Metabolism Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut, Lebanon

Corresponding Author(s) : George Hilal

george.hilal@usj.edu.lb

Cellular and Molecular Biology, Vol. 65 No. 7: Issue 7

Abstract

Aerobic glycolysis, known as the "Warburg effect”, is one of several hallmarks of cancer cells. The conversion of phosphoenolpyruvate (PEP) to pyruvate can be down regulated by the re-expression of the embryonic isoform 2 of pyruvate kinase (PKM2). This mechanism allows the accumulation of glycolytic intermediates for the biosynthesis of macromolecules, such as proteins, lipids and nucleic acids. PKM2 is favored by the well-known PI3K/Akt/mTOR proliferative pathway. This pathway is induced by high glucose levels, and the mTOR kinase is the central activator of the Warburg effect. In this study, we investigated the role of glucose restriction (GR) and mTOR inhibition  in reversing the Warburg effect in MDA-MB 231 and MCF-7 breast cancer cell lines. PKM2 expression was measured by western blot. Lactate production by cells was determined by a colorimetric assay. The concentration of glucose in the supernatant of cells was measured using the Trinder method. ATP level  was evaluated by using a Colorimetric/Fluorometric ATP Assay Kit. Our results showed that MDA-MB 231 cells increased glucose consumption when the glucose concentration was 0 g/L (P <0.01). In MCF-7 cells, glucose deprivation reduced lactate secretion by 80% (P =0.0001) but tripled glucose consumption (P = 0.0041). ATP concentration increased approximately when MCF-7 cells were deprived of glucose (P = 0.02). GSK1059615 does not significantly modulate lactate secretion and glucose uptake in both cell lines. Glucose restriction contribute to the reduction of the Warburg effect through mTOR inhibition and regulation of PKM2 kinases.

Keywords

Glucose restriction PKM2 mTOR MDA-MB 231 MCF-7 GSK1059615.
Tahtouh, R., Wardi, L., Sarkis, R., Hachem, R., Raad, I., El Zein, N., & Hilal, G. (2019). Glucose restriction reverses the Warburg effect and modulates PKM2 and mTOR expression in breast cancer cell lines. Cellular and Molecular Biology, 65(7), 26–33. https://doi.org/10.14715/cmb/2019.65.7.6
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