Linked Life Data

18032574

Source:http://linkedlifedata.com/resource/pubmed/id/18032574

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-1-25
pubmed:abstractText
Age-related macular degeneration (ARMD) is a leading cause of blindness. The major reason for severe vision loss in ARMD is choroidal neovascularization due to an elevation in the expression of angiogenic factors such as vascular endothelial growth factor (VEGF). Drugs with anti-VEGF and antiproliferative activities can be beneficial for the treatment of this disorder. We have previously demonstrated that celecoxib [a selective cyclooxygenase (Cox)-2 inhibitor] inhibits VEGF expression in retinal pigment epithelial cells. In this study, we investigated the antiproliferative effects of celecoxib in adult retinal pigment epithelial (ARPE-19) and choroidal endothelial (RF/6A) cells. The results indicate that celecoxib 1) causes a dose-dependent antiproliferative effect in ARPE-19 and RF/6A cells (IC(50) of 23 and 13 microM, respectively); 2) leads to a G(2)-M phase cell cycle arrest in these cell types; and 3) inhibits VEGF-induced proliferation of RF/6A cells (IC(50) of 20 microM). In addition, 4) the concentrations of celecoxib required for antiproliferative effects are lower than those required for the cytotoxicity. These effects of celecoxib are by mechanisms independent of its Cox-2 inhibitory activity because rofecoxib (another Cox-2 inhibitor) had no effects on the proliferation or cell cycle distribution of the two cell types, and flurbiprofen (an inhibitor of Cox-1 and Cox-2) had weak antiproliferative effects on ARPE-19 cells, with IC(50) of 90 microM. In summary, celecoxib has potent antiproliferative effects in RF/6A and ARPE-19 cells; thus, it can be a potential new treatment in proliferative disorders of the choroid-retina such as choroidal neovascularization in age-related macular degeneration.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1521-0103
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
324
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
749-58
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Celecoxib inhibits proliferation of retinal pigment epithelial and choroid-retinal endothelial cells by a cyclooxygenase-2-independent mechanism.
pubmed:affiliation
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, N.I.H., Extramural