Linked Life Data

20670297

Source:http://linkedlifedata.com/resource/pubmed/id/20670297

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2010-10-18
pubmed:abstractText
Nobiletin is a citrus polymethoxyflavonoid that suppresses tumor growth and metastasis, both of which depend on angiogenesis. We recently identified nobiletin as a cell differentiation modulator. Because cell differentiation is a critical event in angiogenesis, it might be possible that nobiletin could exhibit antiangiogenic activity, resulting in suppression of these tumor malignant properties. To verify this possibility, we examined the antiangiogenic effects of nobiletin in vitro and in vivo. Nobiletin had concentration-dependent inhibitory effects on multiple functions of angiogenesis-related endothelial cells (EC); it suppressed the proliferation, migration and tube formation on matrigel of human umbilical vein EC (HUVEC) stimulated with endothelial cell growth supplement (ECGS), a mixture of acidic and basic fibroblast growth factors (FGFs). Gelatin zymography and northern blotting revealed that nobiletin suppressed pro-matrix metalloproteinase-2 (proMMP-2) production and MMP-2 mRNA expression in ECGS-stimulated HUVEC. Nobiletin also downregulated cell-associated plasminogen activator (PA) activity and urokinase-type PA mRNA expression. Furthermore, nobiletin inhibited angiogenic differentiation induced by vascular endothelial growth factor and FGF, an in vitro angiogenesis model. This inhibition was accompanied by downregulation of angiogenesis-related signaling molecules, such as extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase, and transcriptional factors (c-Jun and signal transducer and activator of transcription 3), and activation of the caspase pathway. In a chick embryo chorioallantoic membrane assay, nobiletin showed an antiangiogenic activity, the ID(50) value being 10?g (24.9nmol) per egg. These results indicate that nobiletin is a novel antiangiogenic compound that exhibits its activity through combined inhibition of multiple angiogenic EC functions.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1349-7006
pubmed:author
pubmed:copyrightInfo
© 2010 Japanese Cancer Association.
pubmed:issnType
Electronic
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2462-9
pubmed:meshHeading
pubmed-meshheading:20670297-Animals, pubmed-meshheading:20670297-Antioxidants, pubmed-meshheading:20670297-Blotting, Northern, pubmed-meshheading:20670297-Blotting, Western, pubmed-meshheading:20670297-Cell Line, pubmed-meshheading:20670297-Cell Movement, pubmed-meshheading:20670297-Cell Proliferation, pubmed-meshheading:20670297-Chick Embryo, pubmed-meshheading:20670297-Chorioallantoic Membrane, pubmed-meshheading:20670297-Dose-Response Relationship, Drug, pubmed-meshheading:20670297-Endothelial Cells, pubmed-meshheading:20670297-Enzyme Precursors, pubmed-meshheading:20670297-Fibroblast Growth Factor 2, pubmed-meshheading:20670297-Flavones, pubmed-meshheading:20670297-Gene Expression, pubmed-meshheading:20670297-Humans, pubmed-meshheading:20670297-Matrix Metalloproteinase 2, pubmed-meshheading:20670297-Neovascularization, Pathologic, pubmed-meshheading:20670297-Neovascularization, Physiologic, pubmed-meshheading:20670297-Plasminogen Activators, pubmed-meshheading:20670297-Signal Transduction, pubmed-meshheading:20670297-Urokinase-Type Plasminogen Activator, pubmed-meshheading:20670297-Vascular Endothelial Growth Factor A
pubmed:year
2010
pubmed:articleTitle
Nobiletin, a citrus polymethoxyflavonoid, suppresses multiple angiogenesis-related endothelial cell functions and angiogenesis in vivo.
pubmed:affiliation
Department of Applied Biological Science, Tokyo University of Science, Chiba Institute for World Health Development, Mukogawa Women's University, Hyogo Tokyo, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't