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Type: Journal article
Title: Short-chain fatty acids induce apoptosis in colon cancer cells associated with changes to intracellular redox state and glucose metabolism
Author: Matthews, G.
Howarth, G.
Butler, R.
Citation: Chemotherapy, 2012; 58(2):102-109
Publisher: Karger
Issue Date: 2012
ISSN: 0009-3157
Statement of
Matthews G.M., Howarth G.S., Butler R.N.
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.
Keywords: Butyrate; Propionate; Short-chain fatty acid; Colon cancer; Apoptosis; Cell cycle; Redox; Glucose metabolism
Rights: Copyright © 2012 S. Karger AG, Basel
RMID: 0020120586
DOI: 10.1159/000335672
Appears in Collections:Animal and Veterinary Sciences publications

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