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Metabolites 2016, 6(4), 33;

The Redox Status of Cancer Cells Supports Mechanisms behind the Warburg Effect

Laboratoire d’Informatique de l’Ecole Polytechnique–Unité Mixte de Recherche 7161, Ecole Polytechnique, Palaiseau 91128, France
Imen Pharmed Iranian Company (IPI), Tehran 1514633711, Iran
Nosco Pharmaceuticals, Paris 75015, France
Laboratoire de Recherche en Informatique (LRI), Université Paris-Sud, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8623, Orsay 91190, France
MaIAGE, INRA, Université Paris-Saclay, Jouy-en-Josas 78350, France
Institute of Translationnal Neurosciences (IHU-A-Institut du Cerveau et de la Moelle Epinière), Pitié Salpêtrière Hospital, Paris 75013, France
Authors to whom correspondence should be addressed.
Received: 12 August 2016 / Accepted: 27 September 2016 / Published: 3 October 2016
PDF [1597 KB, uploaded 10 October 2016]


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. View Full-Text
Keywords: redox oscillators; Warburg effect; cancer disease; mitochondria; central carbon metabolism redox oscillators; Warburg effect; cancer disease; mitochondria; central carbon metabolism

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Moreira, J.D.V.; Hamraz, M.; Abolhassani, M.; Bigan, E.; Pérès, S.; Paulevé, L.; Nogueira, M.L.; Steyaert, J.-M.; Schwartz, L. The Redox Status of Cancer Cells Supports Mechanisms behind the Warburg Effect. Metabolites 2016, 6, 33.

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