title: Green tea phenolics inhibit butyrate-induced differentiation of colon cancer cells by interacting with monocarboxylate transporter 1.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, IBUB, Faculty of Biology, Universitat de Barcelona and Unit Associated with CSIC, 08028 Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain. Electronic address: ssanchezt@ub.edu.
authors.forename: S
authors.initials: S
authors.lastname: Sánchez-Tena
authors.forename: P
authors.initials: P
authors.lastname: Vizán
authors.forename: P K
authors.initials: PK
authors.lastname: Dudeja
authors.forename: J J
authors.initials: JJ
authors.lastname: Centelles
authors.forename: M
authors.initials: M
authors.lastname: Cascante
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000469:Alkaline Phosphatase / Q000378:metabolism; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D020148:Butyric Acid / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006633:Histamine Antagonists / Q000494:pharmacology; D006801:Humans; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism*; D059808:Polyphenols / Q000494:pharmacology*; D013662:Tea / Q000737:chemistry*; D014407:Tumor Cells, Cultured
chemical_list: D016588:Anticarcinogenic Agents; D006633:Histamine Antagonists; D027501:Monocarboxylic Acid Transporters; D059808:Polyphenols; D013662:Tea; D020148:Butyric Acid; D002392:Catechin; C045651:epigallocatechin gallate; D000469:Alkaline Phosphatase
keywords: (−)-epicatechin; (−)-epigallocatechin gallate; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; AP; Butyrate; Colon cancer; Differentiation; EC; EGCG; Epicatechin; Epigallocatechin gallate; HDAC; MCT1; MTT; NaB; TSA; alkaline phosphatase; butyrate; histone deacetylase; monocarboxylate transporter 1; trichostatin A