Linked Life Data

20233901

Source:http://linkedlifedata.com/resource/pubmed/id/20233901

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-4-6
pubmed:abstractText
Nontoxic small molecules with multitargeting effects are believed to have potential in cancer prevention. Dietary phytochemicals were shown to exhibit cancer-preventive effects attributed to their antioxidant capacities. In this report, we show that the natural compound 5-deoxykaempferol (5-DK) exerts a chemopreventive effect on UVB-induced skin carcinogenesis by targeting multiple signaling molecules. 5-DK suppressed the UVB-induced expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor in mouse skin epidermal JB6 P+ cells. Moreover, 5-DK inhibited phosphorylation of MKK3/6, MKK4, and Akt, but had no effect on phosphorylation of Src, extracellular signal-regulated kinases, or ribosomal S6 kinase (RSK). However, 5-DK affected multiple targets by reducing Src, phosphoinositide 3-kinase (PI3K), and RSK2 activities. In particular, pull-down assays revealed that 5-DK specifically bound to and competed with ATP for binding with Src, PI3K, and RSK2. Exposure to 5-DK significantly suppressed UVB-induced tumorigenesis in mouse skin in a dose-dependent manner, and it inhibited the UVB-induced expression of COX-2, proliferating cell nuclear antigen, vascular endothelial growth factor, and matrix metalloproteinase-9. Our data suggest that 5-DK docks at the ATP-binding site of Src, PI3K, and RSK2. For RSK2, the ATP-binding site is located between the N- and C-lobes of the kinase domain. Taken together, our results indicate that 5-DK holds promise for the treatment of UVB-induced skin cancer by targeting Src, PI3K, and RSK2 signaling.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1940-6215
pubmed:author
pubmed:copyrightInfo
(c) 2010 AACR.
pubmed:issnType
Electronic
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
454-65
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:20233901-Animals, pubmed-meshheading:20233901-Antineoplastic Agents, pubmed-meshheading:20233901-Blotting, Western, pubmed-meshheading:20233901-Cyclooxygenase 2, pubmed-meshheading:20233901-Fabaceae, pubmed-meshheading:20233901-Flavonoids, pubmed-meshheading:20233901-Gene Expression, pubmed-meshheading:20233901-Immunohistochemistry, pubmed-meshheading:20233901-Kaempferols, pubmed-meshheading:20233901-Mice, pubmed-meshheading:20233901-Mice, Hairless, pubmed-meshheading:20233901-Phosphatidylinositol 3-Kinases, pubmed-meshheading:20233901-Phytotherapy, pubmed-meshheading:20233901-Plant Extracts, pubmed-meshheading:20233901-Ribosomal Protein S6 Kinases, 90-kDa, pubmed-meshheading:20233901-Signal Transduction, pubmed-meshheading:20233901-Skin Neoplasms, pubmed-meshheading:20233901-Vascular Endothelial Growth Factor A, pubmed-meshheading:20233901-src-Family Kinases
pubmed:year
2010
pubmed:articleTitle
5-deoxykaempferol plays a potential therapeutic role by targeting multiple signaling pathways in skin cancer.
pubmed:affiliation
Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural