title: In vivo relevant mixed urolithins and ellagic acid inhibit phenotypic and molecular colon cancer stem cell features: A new potentiality for ellagitannin metabolites against cancer.
abstract: Colon cancer stem cells (CSCs) offer a novel paradigm for colorectal cancer (CRC) treatment and dietary polyphenols may contribute to battle these cells. Specifically, polyphenol-derived colon metabolites have the potential to interact with and affect colon CSCs. We herein report the effects against colon CSCs of two mixtures of ellagitannin (ET) metabolites, ellagic acid (EA) and the gut microbiota-derived urolithins (Uro) at concentrations detected in the human colon tissues following the intake of ET-containing products (pomegranate, walnuts). These mixtures reduce phenotypic and molecular features in two models of colon CSCs: Caco-2 cells and primary tumour cells from a patient with CRC. The mixture containing mostly Uro-A (85% Uro-A, 10% Uro-C, 5% EA) was most effective at inhibiting the number and size of colonospheres and aldehyde dehydrogenase activity (ALDH, a marker of chemoresistance) whereas the mixture containing less Uro-A but IsoUro-A and Uro-B (30% Uro-A, 50% IsoUro-A, 10% Uro-B, 5% Uro-C, 5% EA) had some effects on the number and size of colonospheres but not on ALDH. These data support a role for polyphenols metabolites in the control of colon cancer chemoresistance and relapse and encourage the research on the effects of polyphenols against CSCs.
authors.affiliation: Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain.
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Núñez-Sánchez
authors.affiliation: Cancer Chemoprevention Group, Department of Cancer Studies, University of Leicester, Leicester, UK.
authors.forename: Ankur
authors.initials: A
authors.lastname: Karmokar
authors.affiliation: Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Sarrías
authors.affiliation: Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: García-Villalba
authors.affiliation: Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain.
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Tomás-Barberán
authors.affiliation: Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain. Electronic address: mtconesa@cebas.csic.es.
authors.forename: María Teresa
authors.initials: MT
authors.lastname: García-Conesa
authors.affiliation: Cancer Chemoprevention Group, Department of Cancer Studies, University of Leicester, Leicester, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Brown
authors.affiliation: Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain. Electronic address: jcespin@cebas.csic.es.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Espín
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003374:Coumarins / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004610:Ellagic Acid / Q000494:pharmacology*; D006801:Humans; D047348:Hydrolyzable Tannins / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D003374:Coumarins; D047348:Hydrolyzable Tannins; C013515:ellagitannin; C026423:3,8-dihydroxy-6H-dibenzo(b,d)pyran-6-one; D004610:Ellagic Acid
keywords: Chemoprevention; Colon cancer; Ellagic acid; Metabotype; Stem cells; Urolithins