Resveratrol에 의한 암 전이 관련 유전자 MMP-9의 발현 조절

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 API and NFkB response elements. Resveratrol inhibited PMA-mediated activation of c-Jun N-terminal kinase (JNK) and protein kinase C (PKC)-5 activation. Therefore, we conclude that the inhibitory activities of resveratrol on MMP-9, JNK, and PKC-5 may have therapeutic potential for controlling growth and invasiveness of tumors.

Key Words: Resveratrol, MMP-9, JNK, API,PMA