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

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.

CHLOROGENIC acid; METABOLITES; APOPTOSIS; COLON cancer; BENZOIC acid; CAFFEIC acid

International Journal of Molecular Sciences, 2018, Vol 19, Issue 3, p723

1661-6596

Academic Journal

10.3390/ijms19030723