Butyrate elicits a metabolic switch in human colon cancer cells by targeting the pyruvate dehydrogenase complex

  title={Butyrate elicits a metabolic switch in human colon cancer cells by targeting the pyruvate dehydrogenase complex},
  author={Jean-Marc Blouin and Graziella Penot and Martine Collinet and Magali Nacfer and Claude Forest and Pierre Laurent-Puig and Xavier Coumoul and Robert Barouki and Chantal Benelli and Sylvie Bortoli},
  journal={International Journal of Cancer},
Butyrate, a short‐chain fatty acid produced by the colonic bacterial fermentation is able to induce cell growth inhibition and differentiation in colon cancer cells at least partially through its capacity to inhibit histone deacetylases. Since butyrate is expected to impact cellular metabolic pathways in colon cancer cells, we hypothesize that it could exert its antiproliferative properties by altering cellular metabolism. We show that although Caco2 colon cancer cells oxidized both butyrate… 


It is hypothesized that SCFA can dampen the inflammatory activity of DETC, the innate resident skin γδ T cell population, by affecting the energy metabolism and inflammatory potential of dendritic epidermal T cells.

Butyrate Alters Pyruvate Flux and Induces Lipid Accumulation in Cultured Colonocytes

The results indicate that butyrate itself is not oxidized in cultured cells but instead alters pyruvate flux and induces lipid accumulation.

Colon cancer cell differentiation by sodium butyrate modulates metabolic plasticity of Caco-2 cells via alteration of phosphotransfer network

The view that modulating cell metabolism through NaBT can be an effective strategy for treating CRC is supported, which indicates a close relationship between the phosphotransfer performance and metabolic plasticity of CRC, which is associated with the cell differentiation state.

Regulation of Butyrate-Induced Resistance through AMPK Signaling Pathway in Human Colon Cancer Cells

Chronic exposure to butyrates increased butyrate resistance in human colon cancer by inducing protective autophagy through the downregulation of AMPK/ACC and activation of Akt/mTOR signaling.

Butyrate and colorectal cancer: the role of butyrate transport.

The mechanisms of BT transport are discussed and this knowledge is integrated with the effects of BT in tumoral and normal colonocytes and the "BT paradox" is integrated.

Butyrate Histone Deacetylase Inhibitors

Efforts to exploit the potential of butyrate in the clinical treatment of cancer and other medical disorders are thwarted by its poor pharmacological properties and the multigram doses needed to achieve therapeutic concentrations in vivo.

Resveratrol reverses the Warburg effect by targeting the pyruvate dehydrogenase complex in colon cancer cells

It is demonstrated that resveratrol induces both a cell growth arrest and a metabolic reprogramming in colon cancer cells, suggesting that res veratrol might improve the oxidative capacities of cancer cells through the CamKKB/AMPK pathway.

Butyrate suppresses proliferation and migration of RKO colon cancer cells though regulating endocan expression by MAPK signaling pathway.

  • L. ZuoMan LuQing ZhouWei WeiY. Wang
  • Biology
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 2013

Microbiota-derived butyrate is an endogenous HIF prolyl hydroxylase inhibitor

The results suggest that the co-evolution of mammals and mutualistic microbiota has selected for butyrate to impact a critical gene regulation pathway that can be extended beyond the mammalian gut.



Butyrate metabolism upstream and downstream acetyl-CoA synthesis and growth control of human colon carcinoma cells.

The data strongly suggest that butyrate acts upon colon carcinoma cells upstream of acetyl-CoA synthesis, and oxidation in the tricarboxylic acid (TCA) cycle and lipid synthesis] likely acts as a regulator ofbutyrate intracellular concentration.

Butyrate metabolism in human colon carcinoma cells: Implications concerning its growth‐inhibitory effect

It is concluded that the metabolism ofbutyrate downstream acetyl‐CoA synthesis is not involved in the butyrate antiproliferative effect and the suggestion that butyrATE metabolism in mitochondria is not used in these cells as a fuel but acts as a regulator of butyrates free concentrations, is discussed.

The Stable Isotope-based Dynamic Metabolic Profile of Butyrate-induced HT29 Cell Differentiation*

The results suggest that the mechanism by which colon carcinoma cells acquire a differentiated phenotype is through a replacement of glucose for butyrate as the main carbon source for macromolecule biosynthesis and energy production.

Beyond aerobic glycolysis: Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis

Transformed cells exhibit a high rate of glutamine consumption that cannot be explained by the nitrogen demand imposed by nucleotide synthesis or maintenance of nonessential amino acid pools, and glutamine metabolism provides a carbon source that facilitates the cell's ability to use glucose-derived carbon and TCA cycle intermediates as biosynthetic precursors.

Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction

It is reported that the transcriptional regulatory properties of the oncogene Myc coordinate the expression of genes necessary for cells to engage in glutamine catabolism that exceeds the cellular requirement for protein and nucleotide biosynthesis, resulting in the reprogramming of mitochondrial metabolism to depend on glutaminolysis to sustain cellular viability and TCA cycle anapleurosis.

Butyrate and trichostatin A effects on the proliferation/differentiation of human intestinal epithelial cells: induction of cyclin D3 and p21 expression

The data may explain how butyrate acts on cell proliferation/differentiation, and they show that trichostatin A does not reproduce every effect ofbutyrate, mainly because of its shorter half life.

Pyruvate Dehydrogenase Complex Activity Controls Metabolic and Malignant Phenotype in Cancer Cells*

It is shown that inhibition of pyruvate dehydrogenase complex (PDC) activity contributes to the Warburg metabolic and malignant phenotype in human head and neck squamous cell carcinoma and that the buildup of glycolytic metabolites, resulting from high PDK-1 expression, may in turn promote HIF-1 activation, thus sustaining a feed-forward loop for malignant progression.

Fuel utilization in colonocytes of the rat.

In incubated colonocytes isolated from rat colons, the rates of utilization O2, glucose or glutamine were linear with respect to time for over 30 min, and the concentrations of adenine nucleotides

Induction of Pyruvate Dehydrogenase Kinase-3 by Hypoxia-inducible Factor-1 Promotes Metabolic Switch and Drug Resistance*

It is reported that hypoxia-inducible factor-1 induced pyruvate dehydrogenase kinase-3 (PDK3) expression leading to inhibition of mitochondrial respiration, and increased PDK3 expression due to elevated HIF-1α in cancer cells may play critical roles in metabolic switch during cancer progression and chemoresistance in cancer therapy.