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https://hdl.handle.net/2440/76681
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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: international journal of experimental and clinical chemotherapy, 2012; 58(2):102-109 |
Publisher: | Karger |
Issue Date: | 2012 |
ISSN: | 0009-3157 1421-9794 |
Statement of Responsibility: | 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 |
DOI: | 10.1159/000335672 |
Published version: | http://dx.doi.org/10.1159/000335672 |
Appears in Collections: | Animal and Veterinary Sciences publications Aurora harvest |
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