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

Sadeghi Ekbatan, Shima; Li, Xiu-Qing; Ghorbani, Mohammad; Azadi, Behnam; Kubow, Stan

doi:10.3390/ijms19030723

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

Shima Sadeghi Ekbatan

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School of Human Nutrition, McGill University, 21111 Lakeshore, Ste Anne de Bellevue, Montreal, QC H9X 3V9, Canada

Fredericton Research and Development Center, Agriculture and Agri-Food Canada, Fredericton, NB E3B 4Z7, Canada

The Rosalind & Morris Goodman Cancer Research Center, McGill University, 1160 Pine Ave West, Montreal, QC H3A 1A3, Canada

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

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

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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. https://doi.org/10.3390/ijms19030723

AMA Style

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. International Journal of Molecular Sciences. 2018; 19(3):723. https://doi.org/10.3390/ijms19030723

Chicago/Turabian Style

Sadeghi Ekbatan, Shima, Xiu-Qing Li, Mohammad Ghorbani, Behnam Azadi, and Stan Kubow. 2018. "Chlorogenic Acid and Its Microbial Metabolites Exert Anti-Proliferative Effects, S-Phase Cell-Cycle Arrest and Apoptosis in Human Colon Cancer Caco-2 Cells" International Journal of Molecular Sciences 19, no. 3: 723. https://doi.org/10.3390/ijms19030723

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

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