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

Behnam Azadi¹  Xiu-Qing Li²  Shima Sadeghi Ekbatan³  Stan Kubow³  Mohammad Ghorbani⁴ 

[1] Morris Goodman Cancer Research Center, McGill University, 1160 Pine Ave West, Montreal, QC H3A 1A3, Canada;Fredericton Research and Development Center, Agriculture and Agri-Food Canada, Fredericton, NB E3B 4Z7, Canada;School of Human Nutrition, McGill University, 21111 Lakeshore, Ste Anne de Bellevue, Montreal, QC H9X 3V9, Canada;;The Rosalind &

关键词: Caco-2 cells;    chlorogenic acid;    caffeic acid;    3-phenylpropionic acid;    benzoic acid;    cell cycle;    caspase-3;    apoptosis;   

DOI  :  10.3390/ijms19030723

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown