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Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models

Tumor chemoresistance is associated with high aerobic glycolysis rates and reduced oxidative phosphorylation, a phenomenon called “Warburg effect” whose reversal could impair the ability of a wide range of cancer cells to survive in the presence or absence of chemotherapy. In previous studies, Short...

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Autores principales: Bianchi, Giovanna, Martella, Roberto, Ravera, Silvia, Marini, Cecilia, Capitanio, Selene, Orengo, Annamaria, Emionite, Laura, Lavarello, Chiara, Amaro, Adriana, Petretto, Andrea, Pfeffer, Ulrich, Sambuceti, Gianmario, Pistoia, Vito, Raffaghello, Lizzia, Longo, Valter D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494906/
https://www.ncbi.nlm.nih.gov/pubmed/25909219
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author Bianchi, Giovanna
Martella, Roberto
Ravera, Silvia
Marini, Cecilia
Capitanio, Selene
Orengo, Annamaria
Emionite, Laura
Lavarello, Chiara
Amaro, Adriana
Petretto, Andrea
Pfeffer, Ulrich
Sambuceti, Gianmario
Pistoia, Vito
Raffaghello, Lizzia
Longo, Valter D.
author_facet Bianchi, Giovanna
Martella, Roberto
Ravera, Silvia
Marini, Cecilia
Capitanio, Selene
Orengo, Annamaria
Emionite, Laura
Lavarello, Chiara
Amaro, Adriana
Petretto, Andrea
Pfeffer, Ulrich
Sambuceti, Gianmario
Pistoia, Vito
Raffaghello, Lizzia
Longo, Valter D.
author_sort Bianchi, Giovanna
collection PubMed
description Tumor chemoresistance is associated with high aerobic glycolysis rates and reduced oxidative phosphorylation, a phenomenon called “Warburg effect” whose reversal could impair the ability of a wide range of cancer cells to survive in the presence or absence of chemotherapy. In previous studies, Short-term-starvation (STS) was shown to protect normal cells and organs but to sensitize different cancer cell types to chemotherapy but the mechanisms responsible for these effects are poorly understood. We tested the cytotoxicity of Oxaliplatin (OXP) combined with a 48hour STS on the progression of CT26 colorectal tumors. STS potentiated the effects of OXP on the suppression of colon carcinoma growth and glucose uptake in both in vitro and in vivo models. In CT26 cells, STS down-regulated aerobic glycolysis, and glutaminolysis, while increasing oxidative phosphorylation. The STS-dependent increase in both Complex I and Complex II-dependent O(2) consumption was associated with increased oxidative stress and reduced ATP synthesis. Chemotherapy caused additional toxicity, which was associated with increased succinate/Complex II-dependent O(2) consumption, elevated oxidative stress and apoptosis. These findings indicate that the glucose and amino acid deficiency conditions imposed by STS promote an anti-Warburg effect characterized by increased oxygen consumption but failure to generate ATP, resulting in oxidative damage and apoptosis.
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spelling pubmed-44949062015-07-13 Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models Bianchi, Giovanna Martella, Roberto Ravera, Silvia Marini, Cecilia Capitanio, Selene Orengo, Annamaria Emionite, Laura Lavarello, Chiara Amaro, Adriana Petretto, Andrea Pfeffer, Ulrich Sambuceti, Gianmario Pistoia, Vito Raffaghello, Lizzia Longo, Valter D. Oncotarget Priority Research Paper Tumor chemoresistance is associated with high aerobic glycolysis rates and reduced oxidative phosphorylation, a phenomenon called “Warburg effect” whose reversal could impair the ability of a wide range of cancer cells to survive in the presence or absence of chemotherapy. In previous studies, Short-term-starvation (STS) was shown to protect normal cells and organs but to sensitize different cancer cell types to chemotherapy but the mechanisms responsible for these effects are poorly understood. We tested the cytotoxicity of Oxaliplatin (OXP) combined with a 48hour STS on the progression of CT26 colorectal tumors. STS potentiated the effects of OXP on the suppression of colon carcinoma growth and glucose uptake in both in vitro and in vivo models. In CT26 cells, STS down-regulated aerobic glycolysis, and glutaminolysis, while increasing oxidative phosphorylation. The STS-dependent increase in both Complex I and Complex II-dependent O(2) consumption was associated with increased oxidative stress and reduced ATP synthesis. Chemotherapy caused additional toxicity, which was associated with increased succinate/Complex II-dependent O(2) consumption, elevated oxidative stress and apoptosis. These findings indicate that the glucose and amino acid deficiency conditions imposed by STS promote an anti-Warburg effect characterized by increased oxygen consumption but failure to generate ATP, resulting in oxidative damage and apoptosis. Impact Journals LLC 2015-03-18 /pmc/articles/PMC4494906/ /pubmed/25909219 Text en Copyright: © 2015 Bianchi et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Priority Research Paper
Bianchi, Giovanna
Martella, Roberto
Ravera, Silvia
Marini, Cecilia
Capitanio, Selene
Orengo, Annamaria
Emionite, Laura
Lavarello, Chiara
Amaro, Adriana
Petretto, Andrea
Pfeffer, Ulrich
Sambuceti, Gianmario
Pistoia, Vito
Raffaghello, Lizzia
Longo, Valter D.
Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models
title Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models
title_full Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models
title_fullStr Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models
title_full_unstemmed Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models
title_short Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models
title_sort fasting induces anti-warburg effect that increases respiration but reduces atp-synthesis to promote apoptosis in colon cancer models
topic Priority Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494906/
https://www.ncbi.nlm.nih.gov/pubmed/25909219
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