title: Epicatechin gallate impairs colon cancer cell metabolic productivity.
abstract: Green tea and grape phenolics inhibit cancer growth and modulate cellular metabolism. Targeting the tumor metabolic profile is a novel therapeutic approach to inhibit cancer cell proliferation. Therefore, we treated human colon adenocarcinoma HT29 cells with the phenolic compound epicatechin gallate (ECG), one of the main catechins in green tea and the most important catechin in grape extracts, and evaluated its antiproliferation effects. ECG reduced tumor viability and induced apoptosis, necrosis, and S phase arrest in HT29 cells. Later, biochemical determinations combined with mass isotopomer distribution analysis using [1,2-(13)C2]-D-glucose as a tracer were used to characterize the metabolic network of HT29 cells in response to different concentrations of ECG. Glucose consumption was importantly decreased after ECG treatment. Moreover, metabolization of [1,2-(13)C2]-D-glucose indicated that the de novo synthesis of fatty acids and the pentose phosphate pathway were reduced in ECG-treated cells. Interestingly, ECG inhibited the activity of transketolase and glucose-6-phosphate dehydrogenase, the key enzymes of the pentose phosphate pathway. Our data point to ECG as a promising chemotherapeutic agent for the treatment of colon cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Sánchez-Tena
authors.forename: Gema
authors.initials: G
authors.lastname: Alcarraz-Vizán
authors.forename: Silvia
authors.initials: S
authors.lastname: Marín
authors.forename: Josep Lluís
authors.initials: JL
authors.lastname: Torres
authors.forename: Marta
authors.initials: M
authors.lastname: Cascante
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D013662:Tea / Q000737:chemistry; D014174:Transketolase / Q000037:antagonists & inhibitors / Q000378:metabolism; D027843:Vitis / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D013662:Tea; D002392:Catechin; C062669:epicatechin gallate; D005954:Glucosephosphate Dehydrogenase; D014174:Transketolase; D005947:Glucose