RepressionofmatrixmetalloproteinasegeneexpressionbyginsenosideRh2inhumanastrogliomacells.docVIP

b i o c h e m i c a l p h a r m a c o l o g y 7 4 2 0 0 7 1 6 4 2 – 1 6 5 1 a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / b i o c h e m p h a r m Repression of matrix metalloproteinase gene expression by ginsenoside Rh2 in human astroglioma cells So-Young Kima, Dong-Hyun Kimb, Sang-Jun Hanb, Jin-Won Hyunc, Hee-Sun Kima,* a Department of Neuroscience and Medical Research Institute, College of Medicine, Ewha Womans University, Mok-6-dong 911-1, Yangchun-Ku, Seoul 158-710, Republic of Korea b Department of Microbial Chemistry, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea c Department of Biochemistry, College of Medicine, Cheju National University, Jeju, Republic of Korea a r t i c l e i n f o Article history: Received 25 June 2007 Accepted 14 August 2007 Keywords: Rh2 Glioma invasion MMP NF-kB AP-1 MAP kinases  a b s t r a c t Matrix metalloproteinases MMPs play an important role in glioma in?ltration, facilitating cell migration and tumor invasion through their ability to degrade the extracellular matrix. Therefore, the inhibition of MMPs has been suggested to be a promising therapeutic strategy for brain tumors. This study examined the effect of ginsenoside Rh2 on the expression of MMPs in human astroglioma cells. Rh2 inhibited the PMA-induced mRNA expression of MMP-1, -3, -9, and -14, suggesting that Rh2 has a broad-spectrum inhibitory effect on MMPs. The molecular mechanism underlying MMP-9 inhibition was further investigated because MMP-9 plays a major role in the invasiveness of glioma. It was found that Rh2 inhibited the secretion and protein expression of MMP-9 induced by PMA in human astroglioma cells. The Rh2-mediated inhibition of MMP-9 gene expression appears to occur through NF-kB and AP- 1 because their DNA binding and transcriptional activities were suppressed by the agent. Furthermore, Rh2 signi?cantly repressed the PMA-mediate