Linked Life Data

17183061

Source:http://linkedlifedata.com/resource/pubmed/id/17183061

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-6-4
pubmed:abstractText
n-3 Polyunsaturated fatty acids have been shown to powerfully inhibit the growth of colon cancer cells, mainly acting as pro-apoptotic agents through inhibition of cycloxygenase-2 (COX-2) expression. Since dysregulation of beta-catenin expression is frequently found at early stage of colorectal carcinogenesis, we analyzed whether docosahexaenoic acid (DHA) may modify the expression of beta-catenin in colon cancer cells (SW480 and HCT116) over-expressing this protein, but lacking COX-2. Futhermore, we investigated if alterations in beta-catenin expression may be associated with apoptosis induction. Treatment of cells with increasing concentrations of DHA induced a dose- and time-dependent inhibition of beta-catenin protein expression which, however, was not accompanied by modifications in beta-catenin transcription. Conversely, the proteasomal inhibitors MG132 and lactacystin prevented DHA-induced beta-catenin decrease, suggesting that DHA may regulate the proteasomal degradation of beta-catenin. The reduced levels of beta-catenin were accompanied by decreased translocation of beta-catenin into the nucleus, where it acts as a transcription factor in concert with T-Cell Factor (TCF). DHA, at the same range of concentrations, was also able to induce apoptosis by a caspase-3-dependent mechanism and to cause a dose- and time-dependent decrease of survivin, an apoptosis inhibitor undetectable in normal tissues and expressed in colorectal cancer through TCF-beta-catenin stimulation. Several other proteins regulated by the TCF-beta-catenin pathway and involved in regulation of tumor growth were down-regulated by DHA, including peroxisome proliferator-activated receptor-delta, membrane type 1 (MT1)-matrix metalloproteinase (MMP), MMP-7 and vascular endothelial growth factor. The present study, thus, raises the possibility that DHA may exert pro-apoptotic and antitumoral effects through proteasomal regulation of beta-catenin levels and alterations in the expression of TCF-beta-catenin target genes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1202-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Docosahexaenoic acid induces proteasome-dependent degradation of beta-catenin, down-regulation of survivin and apoptosis in human colorectal cancer cells not expressing COX-2.
pubmed:affiliation
Institute of General Pathology, Institute of Human Anatomy, Catholic University, Rome, Italy. g.calviello@rm.unicatt.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't