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

• Published in: International journal of molecular sciences Vol. 19; no. 3; p. 723
• Main Authors: Sadeghi Ekbatan, Shima, Li, Xiu-Qing, Ghorbani, Mohammad, Azadi, Behnam, Kubow, Stan
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03-03-2018; MDPI
• Subjects: 3-phenylpropionic acid; Acids; Antiproliferatives; Apoptosis; Benzoic acid; Caco-2 cells; Caffeic acid; Caspase; Caspase-3; cell cycle; Cell growth; Cell proliferation; Chlorogenic acid; Colon; Colon cancer; Colorectal cancer; Cytotoxicity; Deoxyribonucleic acid; DNA; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Metabolites; Microorganisms; Mitochondrial DNA; 3-phenylpropionic acid; Caco-2 cells; cell cycle; chlorogenic acid; apoptosis; benzoic acid; caffeic acid; caspase-3
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19030723

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% (EC
) was lower for MIX (431 ± 51.84 µM) and CA (460 ± 21.88) versus CGA (758 ± 19.09 µM). The EC
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.