J Bacteriol Virol.  2003 Sep;33(3):235-243.

Expressional Regulation of Cancer Metastasis Related Gene, MMP-9, by Resveratrol

• Woo JH
• Kim YH
• Baek WK
• Suh SI
• Suh MH
• Park JW
• Kwon TK

Abstract

Proteolytic degradation of the extracellular matrix and tumor metastasis correlate with the expression of endopeptidases known as matrix metalloproteinases (MMPs). 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 of MMP-9 expression and activity. These effects of resveratrol were dose-dependent and correlated with the suppression of MMP-9 mRNA expression levels. PMA caused a 23-fold increase in MMP-9 promoter activity, which was suppressed by resveratrol. Transient transfection by MMP-9 constructs, in which specific transcriptional factors were mutagenized, indicated that the effects of PMA and resveratrol were mediated via AP1 and NFkB response elements. Resveratrol inhibited PMA-mediated activation of c-Jun Nterminal kinase (JNK) and protein kinase C (PKC)-delta activation. Therefore, we conclude that the inhibitory activities of resveratrol on MMP-9, JNK, and PKC-delta may have therapeutic potential for controlling growth and invasiveness of tumors.

Keyword

Resveratrol; MMP-9; JNK; AP1; PMA

MeSH Terms

Cytokines
Endopeptidases
Extracellular Matrix
Matrix Metalloproteinases
Neoplasm Metastasis*
Phosphotransferases
Protein Kinase C
Response Elements
RNA, Messenger
Signal Transduction
Tetradecanoylphorbol Acetate
Transfection
Vitis
Cytokines
Endopeptidases
Matrix Metalloproteinases
Phosphotransferases
Protein Kinase C
RNA, Messenger
Tetradecanoylphorbol Acetate