WNT Inhibitory Activity of Malus Pumila miller cv Annurca and Malus domestica cv Limoncella Apple Extracts on Human Colon-Rectal Cells Carrying Familial Adenomatous Polyposis Mutations
| Autor: | Maria Maisto, Ettore Novellino, Mariano Stornaiuolo, Gennaro Riccio, Giovanni Battista Rossi, Sara Bottone, Gian Carlo Tenore, Nadia Badolati |
|---|---|
| Přispěvatelé: | Riccio, G., Maisto, Maria, Bottone, S., Badolati, N., Rossi, G. B., Tenore, G. C., Stornaiuolo, M., Novellino, E. |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Colorectal cancer chemistry.chemical_compound 0302 clinical medicine Limoncella Apple extract cell growth Wnt Signaling Pathway nutraceuticals lipid transport WNT pathway inhibitors Nutrition and Dietetics unclassified drug Article Wnt signaling pathway Colon cancer Malu Adenomatous Polyposis Coli germline mutation Malus domestica Biochemistry Malus Pumila extract Malus 030220 oncology & carcinogenesis plant extract Nutraceutical Quercetin lcsh:Nutrition. Foods and food supply apple polyphenols high performance liquid chromatography Colon familial adenomatous polyposis colon cancer Adenomatous Polyposis Coli Protein Apple polyphenol lcsh:TX341-641 Biology familial adenomatous polyposi Article Familial adenomatous polyposis 03 medical and health sciences Germline mutation dysplasia Cell Line Tumor medicine Humans controlled study human immunofluorescence cell viability cell culture Plant Extracts Polyphenols homeostasi medicine.disease biology.organism_classification Wnt signaling Molecular biology human tissue In vitro HEK293 Cells cell proliferation 030104 developmental biology chemistry Cell culture Fruit Malus pumila Caco-2 Cells Food Science |
| Zdroj: | Nutrients Nutrients; Volume 9; Issue 11; Pages: 1262 Nutrients, Vol 9, Iss 11, p 1262 (2017) |
| ISSN: | 2072-6643 |
| DOI: | 10.3390/nu9111262 |
| Popis: | Inhibitors of the Wingless-related Integration site (WNT)/β-catenin pathway have recently been under consideration as potential chemopreventive agents against Familial Adenomatous Polyposis (FAP). This autosomal-dominant syndrome is caused by germline mutations in the gene coding for the protein APC and leads to hyperactivation of the WNT/β-catenin signaling pathway, uncontrolled intestinal cell proliferation and formation of adenocarcinomas. The aim of the present work was to: (i) test, on in vitro cultures of cells carrying FAP mutations and on ex vivo biopsies of FAP patients, the WNT inhibitory activity of extracts from two common southern Italian apples, Malus pumila Miller cv. ‘Annurca’ and Malus domestica cv ‘Limoncella’; (ii) identify the mechanisms underpinning their activities and; (iii) evaluate their potency upon gastrointestinal digestion. We here show that both Annurca and Limoncella apple extracts act as WNT inhibitors, mostly thanks to their polyphenolic contents. They inhibit the pathway in colon cells carrying FAP mutations with active dilutions falling in ranges close to consumer-relevant concentrations. Food-grade manufacturing of apple extracts increases their WNT inhibitory activity as result of the conversion of quercetin glycosides into the aglycone quercetin, a potent WNT inhibitor absent in the fresh fruit extract. However, in vitro simulated gastrointestinal digestion severely affected WNT inhibitory activity of apple extracts, as result of a loss of polyphenols. In conclusion, our results show that apple extracts inhibit the WNT pathway in colon cells carrying FAP mutations and represent a potential nutraceutical alternative for the treatment of this pathology. Enteric coating is advisable to preserve the activity of the extracts in the colon-rectal section of the digestive tract. © 2017 by the authors. Licensee MDPI, Basel, Switzerland. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|