title: Short-chain fatty acids induce apoptosis in colon cancer cells associated with changes to intracellular redox state and glucose metabolism.
abstract: BACKGROUND
  Short-chain fatty acids (SCFA) are undergoing increased scrutiny as chemotherapeutics for colon cancer, although a comprehensive understanding of their mode of action is lacking. We investigated candidate SCFA for their capability to modulate apoptosis, cell cycle, intracellular redox state and glucose metabolism in the Caco-2 human colon cancer cell line.
  
  
  METHODS
  Caco-2 cells were incubated with butyrate, propionate or a combination of these SCFA (1:1) and assessed by flow cytometry, enzyme activity analysis or by isotope ratio mass spectrometry.
  
  
  RESULTS
  Butyrate and the SCFA combination induced apoptosis and G2-M arrest to a greater extent than propionate alone (p < 0.05). SCFA treatment led to time-dependent alterations to the oxidative pentose pathway, reductions in glutathione availability and increases in levels of reactive oxygen species (p < 0.05) compared with untreated controls. The rate of D-glucose metabolism was increased by all SCFA, although to the greatest extent by butyrate (p < 0.05).
  
  
  CONCLUSIONS
  These results suggest that butyrate, or the combination of both SCFA, induced rapid and extensive apoptosis and G2-M arrest associated with changes to redox state and D-glucose metabolism. These results support the potential for butyrate and propionate to act as adjuncts to conventional chemotherapy regimens for colon cancer.
authors.affiliation: Gastroenterology Department, Children, Youth and Women's Health Service, University of Adelaide, S.A., Australia. geoff.matthews@petermac.org
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Matthews
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Howarth
authors.forename: Ross N
authors.initials: RN
authors.lastname: Butler
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002087:Butyrates / Q000494:pharmacology; D018938:Caco-2 Cells; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology; D005232:Fatty Acids, Volatile / Q000494:pharmacology*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects; D010084:Oxidation-Reduction; D011422:Propionates / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D002087:Butyrates; D005232:Fatty Acids, Volatile; D011422:Propionates; D017382:Reactive Oxygen Species; D005978:Glutathione; D005947:Glucose