Effects of Fruit Ellagitannin Extracts, Ellagic Acid, and Their Colonic Metabolite, Urolithin A, on Wnt Signaling
- 16 December 2009
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Agricultural and Food Chemistry
- Vol. 58 (7), 3965-3969
- https://doi.org/10.1021/jf902857v
Abstract
Recent data suggest that ellagitannins (ETs), a class of hydrolyzable tannins found in some fruits and nuts, may have beneficial effects against colon cancer. In the stomach and gut, ETs hydrolyze to release ellagic acid (EA) and are converted by gut microbiota to urolithin A (UA; 3,8-dihydroxy-6H-dibenzopyran-6-one) type metabolites, which may persist in the colon through enterohepatic circulation. However, little is known about the mechanisms of action of either the native compounds or their metabolites on colon carcinogenesis. Components of Wnt signaling pathways are known to play a pivotal role in human colon carcinogenesis, and inappropriate activation of the signaling cascade is observed in 90% of colorectal cancers. This study investigated the effects of UA, EA, and ET-rich fruit extracts on Wnt signaling in a human 293T cell line using a luciferase reporter of canonical Wnt pathway-mediated transcriptional activation. The ET extracts were obtained from strawberry (Fragaria annassa), Jamun berry (Eugenia jambolana), and pomegranate (Punica granatum) fruit and were all standardized to phenolic content (as gallic acid equivalents, GAEs, by the Folin−Ciocalteu method) and to EA content (by high-performance liquid chromatography methods): strawberry = 20.5% GAE, 5.0% EA; Jamun berry = 20.5% GAE, 4.2% EA; pomegranate = 55% GAE, 3.5% EA. The ET extracts (IC50 = 28.0−30.0 μg/mL), EA (IC50 = 19.0 μg/mL; 63 μM), and UA (IC50 = 9.0 μg/mL; 39 μM) inhibited Wnt signaling, suggesting that ET-rich foods have potential against colon carcinogenesis and that urolithins are relevant bioactive constituents in the colon.This publication has 31 references indexed in Scilit:
- Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A in a colitis rat model and the effect of colon inflammation on phenolic metabolism☆The Journal of Nutritional Biochemistry, 2010
- Protein Kinase CK2 in Health and DiseaseCellular and Molecular Life Sciences, 2009
- The dietary hydrolysable tannin punicalagin releases ellagic acid that induces apoptosis in human colon adenocarcinoma Caco-2 cells by using the mitochondrial pathwayThe Journal of Nutritional Biochemistry, 2006
- Identification of Ellagic Acid as Potent Inhibitor of Protein Kinase CK2: A Successful Example of a Virtual Screening ApplicationJournal of Medicinal Chemistry, 2006
- Urolithins, Ellagic Acid-Derived Metabolites Produced by Human Colonic Microflora, Exhibit Estrogenic and Antiestrogenic ActivitiesJournal of Agricultural and Food Chemistry, 2006
- Pomegranate Juice, Total Pomegranate Ellagitannins, and Punicalagin Suppress Inflammatory Cell Signaling in Colon Cancer CellsJournal of Agricultural and Food Chemistry, 2006
- Zebrafish Prickle, a Modulator of Noncanonical Wnt/Fz Signaling, Regulates Gastrulation MovementsCurrent Biology, 2003
- Constitutive Transcriptional Activation by a β-Catenin-Tcf Complex in APC −/− Colon CarcinomaScience, 1997
- The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3.Genes & Development, 1996
- Phenolic substances in grapes and wine, and their significance.1969