Linked Life Data

15688382

Source:http://linkedlifedata.com/resource/pubmed/id/15688382

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-3-31
pubmed:abstractText
Naturally occurring molecules with putative cancer chemopreventive properties such as the phytoalexin resveratrol (3,5,4'-trihydroxystilbene) are lead molecules that guide the design of novel agents with improved pharmacologic properties. The synthetic resveratrol analog 3,4,5,4'-tetramethoxystilbene (DMU-212) has been shown to possess stronger antiproliferative properties in human colon cancer cells than resveratrol. We tested the hypothesis that DMU-212 is also a more potent inhibitor of adenoma development in the Apc(Min+) mouse, a model of human intestinal carcinogenesis. Apc(Min+) mice received either stilbene derivative with the diet (0.2%), and adenomas were counted after experiments were terminated. Resveratrol and DMU-212 decreased adenoma load by 27% and 24%, respectively, compared to untreated controls. Cyclooxygenase (COX) enzymes are important mechanistic targets of resveratrol, and we investigated whether DMU-212 interferes with the expression and activity of COX in human colon cells. Incubation of HCA-7 cancer cells for 24-96 hr with either stilbene derivative (1-50 microM) decreased prostaglandin E-2 (PGE-2) production, but only resveratrol decreased COX-2 protein expression. In mice, which received either stilbene derivative (0.2%) for 3 weeks with their diet, PGE-2 levels in the intestinal mucosa were reduced by between 45% and 62% compared to mice on control diet. While resveratrol inhibited enzyme activity in purified COX preparations, DMU-212 failed to do so. The PGE-2 decrease seen with DMU-212 in cells and in vivo is probably mediated via its metabolites. The results suggest that alteration of the resveratrol molecule to generate DMU-212 does not abrogate its ability to decrease adenoma number in Apc(Min+) mice or to interfere with PGE-2 generation in cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 2005 Wiley-Liss, Inc
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
115
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
194-201
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed-meshheading:15688382-Adenoma, pubmed-meshheading:15688382-Animals, pubmed-meshheading:15688382-Antineoplastic Agents, Phytogenic, pubmed-meshheading:15688382-Chemoprevention, pubmed-meshheading:15688382-Colonic Neoplasms, pubmed-meshheading:15688382-Cyclooxygenase 2, pubmed-meshheading:15688382-Diet, pubmed-meshheading:15688382-Dinoprostone, pubmed-meshheading:15688382-Female, pubmed-meshheading:15688382-Genes, APC, pubmed-meshheading:15688382-Intestinal Mucosa, pubmed-meshheading:15688382-Male, pubmed-meshheading:15688382-Mice, pubmed-meshheading:15688382-Mice, Inbred C57BL, pubmed-meshheading:15688382-Mice, Knockout, pubmed-meshheading:15688382-Prostaglandin-Endoperoxide Synthases, pubmed-meshheading:15688382-Ribonucleotide Reductases, pubmed-meshheading:15688382-Stilbenes, pubmed-meshheading:15688382-Tissue Distribution
pubmed:year
2005
pubmed:articleTitle
Comparison of the effects of the chemopreventive agent resveratrol and its synthetic analog trans 3,4,5,4'-tetramethoxystilbene (DMU-212) on adenoma development in the Apc(Min+) mouse and cyclooxygenase-2 in human-derived colon cancer cells.
pubmed:affiliation
Cancer Biomarkers and Prevention Group, Department of Cancer Studies, University of Leicester, Leicester, United Kingdom.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't