title: The Redox Status of Cancer Cells Supports Mechanisms behind the Warburg Effect.
abstract: To better understand the energetic status of proliferating cells, we have measured the intracellular pH (pHi) and concentrations of key metabolites, such as adenosine triphosphate (ATP), nicotinamide adenine dinucleotide (NAD), and nicotinamide adenine dinucleotide phosphate (NADP) in normal and cancer cells, extracted from fresh human colon tissues. Cells were sorted by elutriation and segregated in different phases of the cell cycle (G0/G1/S/G2/M) in order to study their redox (NAD, NADP) and bioenergetic (ATP, pHi) status. Our results show that the average ATP concentration over the cell cycle is higher and the pHi is globally more acidic in normal proliferating cells. The NAD+/NADH and NADP+/NADPH redox ratios are, respectively, five times and ten times higher in cancer cells compared to the normal cell population. These energetic differences in normal and cancer cells may explain the well-described mechanisms behind the Warburg effect. Oscillations in ATP concentration, pHi, NAD+/NADH, and NADP+/NADPH ratios over one cell cycle are reported and the hypothesis addressed. We also investigated the mitochondrial membrane potential (MMP) of human and mice normal and cancer cell lines. A drastic decrease of the MMP is reported in cancer cell lines compared to their normal counterparts. Altogether, these results strongly support the high throughput aerobic glycolysis, or Warburg effect, observed in cancer cells.
authors.affiliation: Laboratoire d'Informatique du l'X-Unité Mixte de Recherche 7161, Ecole Polytechnique, Palaiseau 91128, France. daveiga@lix.polytechnique.fr.
authors.forename: Jorgelindo da Veiga
authors.initials: JD
authors.lastname: Moreira
authors.affiliation: Imen Pharmed Iranian Company (IPI), Tehran 1514633711, Iran. mhamraz@ipiranian.com.
authors.forename: Minoo
authors.initials: M
authors.lastname: Hamraz
authors.affiliation: Nosco Pharmaceuticals, Paris 75015, France. mabolhas@noscopharm.fr.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abolhassani
authors.affiliation: Laboratoire d'Informatique du l'X-Unité Mixte de Recherche 7161, Ecole Polytechnique, Palaiseau 91128, France. bigan.erwan@orange.fr.
authors.forename: Erwan
authors.initials: E
authors.lastname: Bigan
authors.affiliation: Laboratoire de Recherche en Informatique (LRI), Université Paris-Sud, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8623, Orsay 91190, France. sabine.peres@lri.fr.|MaIAGE, INRA, Université Paris-Saclay, Jouy-en-Josas 78350, France. sabine.peres@lri.fr.
authors.forename: Sabine
authors.initials: S
authors.lastname: Pérès
authors.affiliation: Laboratoire de Recherche en Informatique (LRI), Université Paris-Sud, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8623, Orsay 91190, France. loic.pauleve@lri.fr.
authors.forename: Loïc
authors.initials: L
authors.lastname: Paulevé
authors.affiliation: Laboratoire d'Informatique du l'X-Unité Mixte de Recherche 7161, Ecole Polytechnique, Palaiseau 91128, France. marcel.levy@psl.aphp.fr.|Institute of Translationnal Neurosciences (IHU-A-Institut du Cerveau et de la Moelle Epinière), Pitié Salpêtrière Hospital, Paris 75013, France. marcel.levy@psl.aphp.fr.
authors.forename: Marcel Levy
authors.initials: ML
authors.lastname: Nogueira
authors.affiliation: Laboratoire d'Informatique du l'X-Unité Mixte de Recherche 7161, Ecole Polytechnique, Palaiseau 91128, France. jean-marc.steyaert@polytechnique.edu.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Steyaert
authors.affiliation: Laboratoire d'Informatique du l'X-Unité Mixte de Recherche 7161, Ecole Polytechnique, Palaiseau 91128, France. laurent.schwartz@polytechnique.edu.
authors.forename: Laurent
authors.initials: L
authors.lastname: Schwartz
keywords: Warburg effect; cancer disease; central carbon metabolism; mitochondria; redox oscillators