The stable isotope-based dynamic metabolic profile of butyrate-induced HT29 cell differentiation.
Stable isotope-based dynamic metabolic profiling is applied in this paper to elucidate the mechanism by which butyrate induces cell differentiation in HT29 cells. We utilized butyrate-sensitive (HT29) cells incubated with [1,2-13C2]glucose or [1,2-13C2]butyrate as single tracers to observe the changes in metabolic fluxes in these cells. In HT29 cells, increasing concentrations of butyrate inhibited glucose uptake, glucose oxidation, and nucleic acid ribose synthesis in a dose-dependent fashion. Glucose carbon utilization for de novo fatty acid synthesis and tricarboxylic acid cycle flux was replaced by butyrate. We also demonstrated that these changes are not present in butyrate-resistant pancreatic adenocarcinoma MIA cells. 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. This provides a better understanding of cell differentiation through metabolic adaptive changes in response to butyrate in HT29 cells, demonstrating that variations in metabolic pathway substrate flow are powerful regulators of tumor cell proliferation and differentiation.
Department of Biochemistry and Molecular Biology, Centre Recerca en Química Teòrica-Parc Cientific de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Martí i Franquès 1, 08028 Barcelona, Catalonia, Spain.
Joan
J
Boren
Wai-Nang Paul
WN
Lee
Sara
S
Bassilian
Josep Joan
JJ
Centelles
Shu
S
Lim
Sayed
S
Ahmed
László G
LG
Boros
Marta
M
Cascante
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000230:Adenocarcinoma / Q000473:pathology*; D002087:Butyrates / Q000378:metabolism / Q000494:pharmacology*; D002247:Carbon Isotopes; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D019073:HT29 Cells; D006801:Humans; D008316:Malonyl Coenzyme A / Q000378:metabolism; D010084:Oxidation-Reduction; D010190:Pancreatic Neoplasms / Q000473:pathology; D010427:Pentose Phosphate Pathway
D002087:Butyrates; D002247:Carbon Isotopes; D008316:Malonyl Coenzyme A; D000105:Acetyl Coenzyme A; D005947:Glucose