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

Giovanna Bianchi, Roberto Martella, Silvia Ravera, Cecilia Marini, Selene Capitanio, Annamaria Orengo, Laura Emionite, Chiara Lavarello, Adriana Amaro, Andrea Petretto, Ulrich Pfeffer, Gianmario Sambuceti, Vito Pistoia, Lizzia Raffaghello, Valter D. Longo

Research output: Contribution to journalArticlepeer-review

Abstract

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 O2 consumption was associated with increased oxidative stress and reduced ATP synthesis. Chemotherapy caused additional toxicity, which was associated with increased succinate/Complex IIdependent O2 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.

Original languageEnglish
Pages (from-to)11806-11819
Number of pages14
JournalOncotarget
Volume6
Issue number14
Publication statusPublished - 2015

Keywords

  • Colon cancer
  • Fasting
  • Glucose uptake
  • Oxidative phosphorylation
  • Warburg effect

ASJC Scopus subject areas

  • Oncology

Fingerprint

Dive into the research topics of 'Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models'. Together they form a unique fingerprint.

Cite this