Linked Life Data

19776176

Source:http://linkedlifedata.com/resource/pubmed/id/19776176

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2009-11-26
pubmed:abstractText
Cyclooxygenase-2 (COX-2), a key mediator of inflammation, and its product, prostaglandin E(2) (PGE(2)), enhance carcinogenesis, particularly in skin. Ultraviolet (UV) B is the most carcinogenic component of solar irradiation, and a crucial role of COX-2 in UVB-mediated skin carcinogenesis has been reported. Here, we investigated the effects of delphinidin, an abundant dietary anthocyanin, on UVB-induced COX-2 upregulation and the underlying molecular mechanism. We found that delphinidin suppressed UVB-induced COX-2 expression in JB6 P+ mouse epidermal cells. COX-2 promoter activity and PGE(2) production were also suppressed by delphinidin treatment within non-cytotoxic concentrations. Activator protein-1 and nuclear factor-kappaB, crucial transcription factors involved in COX-2 expression, were activated by UVB and delphinidin abolished this activation. UVB-induced phosphorylation of c-Jun N-terminal kinase, p38 kinase and Akt was inhibited by delphinidin. The activities of mitogen-activated protein kinase kinase (MAPKK) 4 and phosphatidylinositol-3 kinase (PI-3K) were inhibited markedly by delphinidin. A pull-down assay using delphinidin-Sepharose beads revealed that delphinidin binds directly with MAPKK4 or PI-3K in a manner that was competitive with adenosine triphosphate. Moreover, in vivo investigations using mouse skin revealed that the upregulation of COX-2 expression, MAPKK4 activity and PI-3K activity induced by UVB was abolished with delphinidin treatment. Collectively, our results demonstrated that delphinidin targets MAPKK4 and PI-3K directly to suppress COX-2 overexpression, suggesting a potential protective role for delphinidin against UVB-mediated skin carcinogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1460-2180
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1932-40
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:19776176-Animals, pubmed-meshheading:19776176-Anthocyanins, pubmed-meshheading:19776176-Cells, Cultured, pubmed-meshheading:19776176-Cyclooxygenase 2, pubmed-meshheading:19776176-Dietary Carbohydrates, pubmed-meshheading:19776176-Dinoprostone, pubmed-meshheading:19776176-Enzyme Activation, pubmed-meshheading:19776176-Epidermis, pubmed-meshheading:19776176-Female, pubmed-meshheading:19776176-MAP Kinase Kinase 4, pubmed-meshheading:19776176-Mice, pubmed-meshheading:19776176-Mice, Inbred ICR, pubmed-meshheading:19776176-NF-kappa B, pubmed-meshheading:19776176-Phosphatidylinositol 3-Kinases, pubmed-meshheading:19776176-Skin Neoplasms, pubmed-meshheading:19776176-Transcription Factor AP-1, pubmed-meshheading:19776176-Ultraviolet Rays, pubmed-meshheading:19776176-Up-Regulation
pubmed:year
2009
pubmed:articleTitle
Delphinidin suppresses ultraviolet B-induced cyclooxygenases-2 expression through inhibition of MAPKK4 and PI-3 kinase.
pubmed:affiliation
Major in Biomodulation, Department of Agricultural Biotechnology, Seoul National University, Seoul 151-742, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural