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Ginseng saponin metabolite suppresses phorbol ester–induced matrix metalloproteinase‐9 expression through inhibition of activator protein‐1 and mitogen‐activated protein kinase signaling pathways in human astroglioma cells
Author(s) -
Jung SooHyun,
Woo MoonSook,
Kim SoYoung,
Kim WonKi,
Hyun JinWon,
Kim EunJin,
Kim DongHyun,
Kim HeeSun
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21356
Subject(s) - mapk/erk pathway , p38 mitogen activated protein kinases , matrix metalloproteinase , activator (genetics) , protein kinase c , biology , matrix metalloproteinase inhibitor , kinase , signal transduction , protein kinase a , gene expression , ginseng , cancer research , microbiology and biotechnology , chemistry , biochemistry , medicine , gene , alternative medicine , pathology
Aberrant expression of matrix metalloproteinase‐9 (MMP‐9) is implicated in the process of invasion and angiogenesis of malignant tumors as well as in inflammatory diseases of the CNS. Therefore, the development of compounds that can inhibit or suppress MMP‐9 is required to treat brain tumors. We investigated the effects of a ginseng saponin metabolite, compound K (20‐ O ‐(β‐ D ‐glucopyranosyl)‐20(S)‐protopanaxadiol), on MMP‐9 expression in human astroglioma cells. Compound K significantly inhibited the secretion and protein expression of MMP‐9 induced by PMA. The inhibitory effect of compound K on MMP‐9 expression correlated with decreased MMP‐9 mRNA levels and suppression of MMP‐9 promoter activity. The compound K–mediated inhibition of MMP‐9 gene expression appears to occur via AP‐1 because its DNA‐binding and transcriptional activities were suppressed by the agent. Furthermore, compound K significantly repressed the PMA‐mediated activation of p38 MAPK, ERK and JNK, which are upstream modulators of AP‐1. Finally, compound K inhibited the in vitro invasiveness of glioma cells. Therefore, inhibition of MMP‐9 expression by compound K might have therapeutic potential for controlling the growth and invasiveness of brain tumors. © 2005 Wiley‐Liss, Inc.