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

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.

The Antiglycation Effect of Monomethyl Branched Chained Fatty Acid and Phytochemical Compounds and their Synergistic Effect on Obesity Related Colorectal Cancer Cell Panel

“…Parallel with our antiproliferative results regarding Hydroxycitric Acid, it was observed the antiproliferative activity of citric acid in skin cancer by inducing apoptotic [31], and the antiproliferative activity of hydroxycitrate against lung cancer, bladder cancer, and melanoma [32]. Furthermore, it was reported that Chlorogenic Acid can inhibit the growth of colon cancer and leukemia by inducing cell cycle arrest at S-phase and activating caspase-3 [33].…”

Chlorogenic acid acts upon Leishmania donovani arresting cell cycle and modulating cytokines and nitric oxide in vitro

“…This fact of metabolic activity reduction in many of the stressed but living promastigotes prompted us to assume that beyond leishmanicidal activity there must be additional effects of CGA to arrest the cell cycle of the promastigotes that ultimately resulted in decreased number of promastigotes in treated cultures. Recent reports from two different groups showed the efficacy of CGA to arrest cell cycle of colon cancer cells at S phase 27,28 . Our data for cell cycle analysis, as tracked after 36 hours treatment, showed significant higher accumulation of the CGA treated promastigotes in the G0/G1 phase than observed in untreated cells.…”

Evaluation of the Antioxidant and Wound-Healing Properties of Extracts from Different Parts of Hylocereus polyrhizus

“…Numerous reports have shown that fresh fruits and vegetables have excellent antioxidant constituents and thus they may confer protection against chronic diseases caused by oxidative stress, such as cardiovascular disorders and some kinds of cancer [6][7][8][9][10]. Phenolic and flavonoid compounds have been reported to exhibit antioxidant properties [11].…”