Fasting induces anti-Warburg effect that increases respiration but reduces ATP-synthesis to promote apoptosis in colon cancer models.
Level 5 - mechanism / opinion, no new human data
Preclinical in vitro and in vivo animal research
PubMed 25909219 · doi:10.18632/oncotarget.3688
What was done
Researchers examined the impact of combining a 48-hour short-term starvation (STS) regimen with oxaliplatin on CT26 colorectal tumor growth in both in vitro cell culture and in vivo animal models. They evaluated changes in tumor progression, glucose uptake, aerobic glycolysis, glutaminolysis, oxidative phosphorylation (Complex I and Complex II-dependent oxygen consumption), ATP synthesis, oxidative stress, and apoptosis.
What was found
The abstract reports no numerical values, effect sizes, or statistical metrics. Short-term starvation potentiated oxaliplatin in suppressing tumor growth and glucose uptake across both in vitro and in vivo models. In CT26 cells, STS down-regulated aerobic glycolysis and glutaminolysis while increasing Complex I and Complex II-dependent oxygen consumption; this increased respiration was accompanied by increased oxidative stress and decreased ATP synthesis. Adding chemotherapy further elevated succinate/Complex II-dependent oxygen consumption, oxidative stress, and apoptosis.
Why it matters
This work identifies a mechanism by which nutrient deprivation disrupts cancer cell metabolism, reversing the Warburg effect to cause uncoupled mitochondrial respiration and sensitize colorectal cancer cells to chemotherapy.
Limits
The study is restricted to preclinical in vitro and in vivo models using a single murine cell line (CT26), so relevance to human clinical treatment is unknown. The abstract does not provide sample sizes, quantitative measurements, or variance data.
Cited by
- supports Lowering glucose through fasting forces cancer cells into a fasting-dependent anti-Warburg effect, shifting them toward mitochondrial oxidative phosphorylation and reactive oxygen species generation.