Green tea phenolics inhibit butyrate-induced differentiation of colon cancer cells by interacting with monocarboxylate transporter 1

• Published in: Biochimica et biophysica acta Vol. 1832; no. 12; pp. 2264 - 2270
• Main Authors: Sánchez-Tena, S., Vizán, P., Dudeja, P.K., Centelles, J.J., Cascante, M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2013
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Alkaline Phosphatase - metabolism; Anticarcinogenic Agents - pharmacology; Apoptosis - drug effects; Blotting, Western; Butyrate; Butyric Acid - pharmacology; Catechin - analogs & derivatives; Catechin - pharmacology; Cell Differentiation - drug effects; Cell Membrane - drug effects; Cell Membrane - metabolism; Cell Proliferation - drug effects; Colon cancer; Colonic Neoplasms - drug therapy; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Differentiation; Epicatechin; Epigallocatechin gallate; Histamine Antagonists - pharmacology; Humans; Membrane Microdomains - drug effects; Membrane Microdomains - metabolism; Monocarboxylic Acid Transporters - metabolism; Polyphenols - pharmacology; Tea - chemistry; Tumor Cells, Cultured; TSA; EGCG; MTT; NaB; AP; Epicatechin; Butyrate; Epigallocatechin gallate; Colon cancer; MCT1; Differentiation; EC; HDAC; (−)-epicatechin; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; trichostatin A; monocarboxylate transporter 1; histone deacetylase; (−)-epigallocatechin gallate; alkaline phosphatase
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2013.08.009

Diet has a significant impact on colorectal cancer and both dietary fiber and plant-derived compounds have been independently shown to be inversely related to colon cancer risk. Butyrate (NaB), one of the principal products of dietary fiber fermentation, induces differentiation of colon cancer cell lines by inhibiting histone deacetylases (HDACs). On the other hand, (−)-epicatechin (EC) and (−)-epigallocatechin gallate (EGCG), two abundant phenolic compounds of green tea, have been shown to exhibit antitumoral properties. In this study we used colon cancer cell lines to study the cellular and molecular events that take place during co-treatment with NaB, EC and EGCG. We found that (i) polyphenols EC and EGCG fail to induce differentiation of colon adenocarcinoma cell lines; (ii) polyphenols EC and EGCG reduce NaB-induced differentiation; (iii) the effect of the polyphenols is specific for NaB, since differentiation induced by other agents, such as trichostatin A (TSA), was unaltered upon EC and EGCG treatment, and (iv) is independent of the HDAC inhibitory activity of NaB. Also, (v) polyphenols partially reduce cellular NaB; and (vi) on a molecular level, reduction of cellular NaB uptake by polyphenols is achieved by impairing the capacity of NaB to relocalize its own transporter (monocarboxylate transporter 1, MCT1) in the plasma membrane. Our findings suggest that beneficial effects of NaB on colorectal cancer may be reduced by green tea phenolic supplementation. This valuable information should be of assistance in choosing a rational design for more effective diet-driven therapeutic interventions in the prevention or treatment of colorectal cancer. •Tea phenolics, epicatechin (EC) and epigallocatechin gallate (EGCG) do not vary HT29 differentiation.•EC and EGCG reduce butyrate-induced differentiation in HT29 cells.•EC and EGCG effect is not related to an HDAC-dependent mechanism.•Tea polyphenols reduce butyrate cellular uptake.•EC and EGCG impair the capacity of butyrate to reorganize MCT1 in the plasma membrane.