Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-4-26
pubmed:abstractText
The expression of matrix metalloproteinase-9 (MMP-9) has been implicated in the invasion and metastasis of cancer cells. Here, we found that an antitumor antibiotic, ascofuranone, inhibits invasion and MMP-9 induction induced by phorbol myristate acetate (PMA) in human cell lines. Ascofuranone also inhibits the protein expression and transcription of MMP-9 induced by tumor necrosis factor-alpha. The inhibition of MMP-9 induction was observed in human cancer cell lines as well as primary rat mesangial cells. Furthermore, as evidenced by MMP-9 promoter and electrophoretic mobility shift assays, ascofuranone specifically inhibited MMP-9 gene expression by blocking PMA-stimulated activation of activator protein-1 (AP-1). In addition, ascofuranone suppressed PMA-induced phosphorylation of Ras, Raf, MEK and extracellular signal-regulated kinase (ERK), upstream factors involved in AP-1activation, whereas the phosphorylation of p38 and JNK/mitogen-activated protein kinase was not affected by ascofuranone, suggesting that the primary target of ascofuranone for suppression of the AP-1 induction is present in upstream of ERK signaling pathway. These results suggest that the suppression of MMP-9 expression, at least in part, contributes to the antitumor activity of ascofuranone.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
28
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1104-10
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17114644-Animals, pubmed-meshheading:17114644-Antibiotics, Antineoplastic, pubmed-meshheading:17114644-Enzyme Activation, pubmed-meshheading:17114644-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:17114644-Gene Expression Regulation, Enzymologic, pubmed-meshheading:17114644-Genes, ras, pubmed-meshheading:17114644-Humans, pubmed-meshheading:17114644-MAP Kinase Signaling System, pubmed-meshheading:17114644-Matrix Metalloproteinase 9, pubmed-meshheading:17114644-Rats, pubmed-meshheading:17114644-Sesquiterpenes, pubmed-meshheading:17114644-Signal Transduction, pubmed-meshheading:17114644-Tetradecanoylphorbol Acetate, pubmed-meshheading:17114644-Transcription Factor AP-1, pubmed-meshheading:17114644-Transcriptional Activation, pubmed-meshheading:17114644-Tumor Cells, Cultured, pubmed-meshheading:17114644-raf Kinases
pubmed:year
2007
pubmed:articleTitle
Ascofuranone suppresses PMA-mediated matrix metalloproteinase-9 gene activation through the Ras/Raf/MEK/ERK- and Ap1-dependent mechanisms.
pubmed:affiliation
Department of Pathology, Catholic University of Daegu School of Medicine, 3056-6, Daemyung-4-Dong, Nam-gu, Daegu 705-718, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't