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Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC delta signal transduction

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Author(s)
Young Han LeeJu-Hyung WooJun Hee LimYoung-Ho KimSeong-Il SuhDo Sik MinJong-Soo ChangJong-Wook ParkTaeg Kyu Kwon
Keimyung Author(s)
Park, Jong WookKwon, Taeg KyuSuh, Seong Il
Department
Dept. of Immunology (면역학)
Dept. of Microbiology (미생물학)
Journal Title
Oncogene
Issued Date
2004
Volume
23
Issue
10
Keyword
resveratrolmatrix metalloproteinase-9NF-kBPMAPKCJNK
Abstract
Proteolytic degradation of the extracellular matrix and
tumor metastasis correlate with the expression of
endopeptidases known as matrix metalloproteinases
(MMPs). The expression of MMPs is regulated by
cytokines and signal transduction pathways, including
those activated by phorbol myristate acetate (PMA). We
found that resveratrol, a phytoalexin present in grapes,
significantly inhibits the PMA-induced increase in MMP-
9 expression and activity. These effects of resveratrol are
dose dependent and correlate with the suppression of
MMP-9 mRNA expression levels. PMA caused about a
23-fold increase in MMP-9 promoter activity, which was
suppressed by resveratrol. Transient transfection utilizing
MMP-9 constructs, in which specific transcriptional
factors were mutagenized, indicated that the effects of
PMA and resveratrol were mediated via an activator
protein-1 and nuclear factor-jB response element. Resveratrol
inhibited PMA-mediated activation of c-Jun Nterminal
kinase (JNK) and protein kinase C (PKC)-d
activation. Therefore, we conclude that the MMP-9
inhibition activity of resveratrol and its inhibition of
JNK and PKC-d may have a therapeutic potential, given
that a novel means of controlling growth and invasiveness
of tumors.
Oncogene (2004) 23, 1845–1853 doi:10.1038/sj.onc.1207307
Published online 8 December 2003
Keywords: resveratrol; matrix metalloproteinase-9;
NF-kB; PMA; PKC; JNK
Keimyung Author(s)(Kor)
박종욱
권택규
서성일
Publisher
School of Medicine
Citation
Young Han Lee et al. (2004). Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC delta signal transduction. Oncogene, 23(10), 1845–1853. doi: 10.1038/sj.onc.1207307
Type
Article
ISSN
0950-9232
Source
http://www.nature.com/articles/1207307
DOI
10.1038/sj.onc.1207307
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/33593
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
1. School of Medicine (의과대학) > Dept. of Microbiology (미생물학)
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