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Int. J. Mol. Sci. 2018, 19(3), 723; https://doi.org/10.3390/ijms19030723

Chlorogenic Acid and Its Microbial Metabolites Exert Anti-Proliferative Effects, S-Phase Cell-Cycle Arrest and Apoptosis in Human Colon Cancer Caco-2 Cells

1
School of Human Nutrition, McGill University, 21111 Lakeshore, Ste Anne de Bellevue, Montreal, QC H9X 3V9, Canada
2
Fredericton Research and Development Center, Agriculture and Agri-Food Canada, Fredericton, NB E3B 4Z7, Canada
3
The Rosalind & Morris Goodman Cancer Research Center, McGill University, 1160 Pine Ave West, Montreal, QC H3A 1A3, Canada
*
Author to whom correspondence should be addressed.
Received: 10 February 2018 / Revised: 23 February 2018 / Accepted: 27 February 2018 / Published: 3 March 2018
(This article belongs to the Special Issue Bioactive Phenolics and Polyphenols 2018)
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Abstract

Chlorogenic acid (CGA) decreases colon cancer-cell proliferation but the combined anti-cancer effects of CGA with its major colonic microbial metabolites, caffeic acid (CA), 3-phenylpropionic acid (3-PPA) and benzoic acid (BA), needs elucidation as they occur together in colonic digesta. Caco-2 cancer cells were treated for 24 h with the four compounds individually (50–1000 µM) and as an equimolar ratio (1:1:1:1; MIX). The effective concentration to decrease cell proliferation by 50% (EC50) was lower for MIX (431 ± 51.84 µM) and CA (460 ± 21.88) versus CGA (758 ± 19.09 µM). The EC50 for cytotoxicity measured by lactate dehydrogenase release in MIX (527 ± 75.34 µM) showed more potency than CA (740 ± 38.68 µM). Cell proliferation was decreased by 3-PPA and BA at 1000 µM with no cytotoxicity. Cell-cycle arrest was induced at the S-phase by CA (100 µM), MIX (100 µM), CGA (250 µM) and 3-PPA (500 µM) with activation of caspase-3 by CGA, CA, MIX (500 and 1000 µM). Mitochondrial DNA content was reduced by 3-PPA (1000 µM). The anti-cancer effects occurred at markedly lower concentrations of each compound within MIX than when provided singly, indicating that they function together to enhance anti-colon cancer activities. View Full-Text
Keywords: Caco-2 cells; chlorogenic acid; caffeic acid; 3-phenylpropionic acid; benzoic acid; cell cycle; caspase-3; apoptosis Caco-2 cells; chlorogenic acid; caffeic acid; 3-phenylpropionic acid; benzoic acid; cell cycle; caspase-3; apoptosis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Sadeghi Ekbatan, S.; Li, X.-Q.; Ghorbani, M.; Azadi, B.; Kubow, S. Chlorogenic Acid and Its Microbial Metabolites Exert Anti-Proliferative Effects, S-Phase Cell-Cycle Arrest and Apoptosis in Human Colon Cancer Caco-2 Cells. Int. J. Mol. Sci. 2018, 19, 723.

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