Linked Life Data

16968061

Source:http://linkedlifedata.com/resource/pubmed/id/16968061

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2006-9-13
pubmed:abstractText
Glycogen synthase kinase-3beta (GSK3beta) is one of the key elements of the Wnt pathway involved in the regulation of beta-catenin homeostasis. The inhibition of GSK3beta kinase activity might lead to the onset of beta-catenin/TCF/LEF-mediated gene transcription, representing a potentially mitogenic stimulus. Apple polyphenols have been shown to mediate several biological effects that might be of interest with respect to chemoprevention. The objective of the study was to elucidate whether apple polyphenols also modulate key elements of the Wnt pathway, an effect that might limit the usefulness of these compounds for the prevention of carcinogenesis. A polyphenol-rich apple juice extract (AE02) was found to effectively inhibit the kinase activity of GSK3beta, immunoprecipitated from HT29 cells. Treatment of HT29 cells with AE02 for 24 h resulted in a concentration-dependent decrease of the cellular GSK3beta kinase activity. The inhibition of the kinase activity in HT29 cells was observed at polyphenol concentrations corresponding to the concentration of the constituents in the original apple juice. The apple characteristic dihydrochalcone glycoside phloridzin was found to be inactive up to 500 muM. The free aglycon phloretin as well as the flavonol quercetin effectively inhibited isolated GSK3beta, but did not affect the respective kinase activity within HT29 cells. In accordance with the inhibition of GSK3beta kinase activity by AE02, treatment of HT29 cells resulted in a significant decrease of phosphorylated beta-catenin. However, the total intracellular beta-catenin level was also found to be diminished, indicating that the interference of the apple constituents with GSK3beta was not associated with a stabilization of beta-catenin in HT29 cells. In line with these results, TCF/LEF-mediated gene transcription remained unaffected by treatment with AE02 as shown in a reporter gene approach. We can assume from the results that at consumer-relevant concentrations apple polyphenols do not mediate growth-stimulating effects in HT29 cells via the Wnt pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-8561
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7041-6
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Modulation of key elements of the Wnt pathway by apple polyphenols.
pubmed:affiliation
Institute of Applied Biosciences, Section of Food Toxicology, University of Karlsruhe (TH), Fritz-Haber-Weg 2, 76131 Karlsruhe, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't