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-κB response element. Resveratrol inhibited PMA-mediated activation of c-Jun N-terminal kinase (JNK) and protein kinase C (PKC)-δ activation. Therefore, we conclude that the MMP-9 inhibition activity of resveratrol and its inhibition of JNK and PKC-δ may have a therapeutic potential, given that a novel means of controlling growth and invasiveness of tumors.
| Original language | English |
|---|---|
| Pages (from-to) | 1845-1853 |
| Number of pages | 9 |
| Journal | Oncogene |
| Volume | 23 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2004 Mar 11 |
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All Science Journal Classification (ASJC) codes
- Molecular Biology
- Genetics
- Cancer Research
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Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC δ signal transduction. / Woo, Ju Hyung; Lim, Jun Hee; Kim, Young Ho; Suh, Seong Il; Min, Do Sik; Chang, Jong Soo; Lee, Young Han; Park, Jong Wook; Kwon, Taeg Kyu.
In: Oncogene, Vol. 23, No. 10, 11.03.2004, p. 1845-1853.Research output: Contribution to journal › Article
TY - JOUR
T1 - Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC δ signal transduction
AU - Woo, Ju Hyung
AU - Lim, Jun Hee
AU - Kim, Young Ho
AU - Suh, Seong Il
AU - Min, Do Sik
AU - Chang, Jong Soo
AU - Lee, Young Han
AU - Park, Jong Wook
AU - Kwon, Taeg Kyu
PY - 2004/3/11
Y1 - 2004/3/11
N2 - 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-κB response element. Resveratrol inhibited PMA-mediated activation of c-Jun N-terminal kinase (JNK) and protein kinase C (PKC)-δ activation. Therefore, we conclude that the MMP-9 inhibition activity of resveratrol and its inhibition of JNK and PKC-δ may have a therapeutic potential, given that a novel means of controlling growth and invasiveness of tumors.
AB - 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-κB response element. Resveratrol inhibited PMA-mediated activation of c-Jun N-terminal kinase (JNK) and protein kinase C (PKC)-δ activation. Therefore, we conclude that the MMP-9 inhibition activity of resveratrol and its inhibition of JNK and PKC-δ may have a therapeutic potential, given that a novel means of controlling growth and invasiveness of tumors.
UR - http://www.scopus.com/inward/record.url?scp=1842482424&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1842482424&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1207307
DO - 10.1038/sj.onc.1207307
M3 - Article
C2 - 14661062
AN - SCOPUS:1842482424
VL - 23
SP - 1845
EP - 1853
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 10
ER -