Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2000-8-24
pubmed:abstractText
Although the beneficial effect of cimetidine on survival in cancer has been clinically demonstrated in colorectal cancer patients, the mode of action of cimetidine has not been elucidated. In this report, we have demonstrated for the first time that cimetidine can block the adhesion of a colorectal tumor cell line to the endothelial cell monolayer in cell culture and that it can suppress the metastasis of the tumor cell in a nude mouse model. We also demonstrated that these antimetastasis effects of cimetidine might occur through down-regulation of the cell surface expression of E-selectin on endothelial cells, a ligand for sialyl Lewis antigens on tumor cells. We found that the cimetidine-mediated down-regulation of E-selectin did not involve down-regulation of E-selectin mRNA or blocking of the nuclear translocation of nuclear factor kappaB, a transcriptional activator of E-selectin gene expression. Because two other histamine type 2 receptor antagonists, famotidine and ranitidine, did not show any similar effect, these actions of cimetidine probably do not occur via blocking of the histamine receptor. These observations support the idea that cancer metastasis can be blocked by cimetidine administration through blocking the adhesion of tumor cells to the endothelium when an interaction between E-selectin and sialyl-Lewis antigens plays a role.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3978-84
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10919677-Animals, pubmed-meshheading:10919677-Cell Adhesion, pubmed-meshheading:10919677-Cell Nucleus, pubmed-meshheading:10919677-Cimetidine, pubmed-meshheading:10919677-Colorectal Neoplasms, pubmed-meshheading:10919677-Dose-Response Relationship, Drug, pubmed-meshheading:10919677-Down-Regulation, pubmed-meshheading:10919677-E-Selectin, pubmed-meshheading:10919677-Endothelium, Vascular, pubmed-meshheading:10919677-Enzyme Inhibitors, pubmed-meshheading:10919677-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:10919677-Famotidine, pubmed-meshheading:10919677-Histamine H2 Antagonists, pubmed-meshheading:10919677-Humans, pubmed-meshheading:10919677-Interleukin-1, pubmed-meshheading:10919677-Liver Neoplasms, pubmed-meshheading:10919677-Mice, pubmed-meshheading:10919677-Mice, Nude, pubmed-meshheading:10919677-Microscopy, Confocal, pubmed-meshheading:10919677-NF-kappa B, pubmed-meshheading:10919677-Neoplasm Transplantation, pubmed-meshheading:10919677-Oligosaccharides, pubmed-meshheading:10919677-RNA, Messenger, pubmed-meshheading:10919677-Ranitidine, pubmed-meshheading:10919677-Transcriptional Activation, pubmed-meshheading:10919677-Tumor Cells, Cultured, pubmed-meshheading:10919677-Umbilical Veins
pubmed:year
2000
pubmed:articleTitle
Cimetidine inhibits cancer cell adhesion to endothelial cells and prevents metastasis by blocking E-selectin expression.
pubmed:affiliation
Department of Molecular Genetics, Nagoya City University Medical School, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't