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
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
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DOI：
10.1002/ijc.21356
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发表时间：
2006-01-15
影响因子：
6.4
通讯作者：
Kim, HS
中科院分区：
文献类型：
--
作者：
Jung, SH;Woo, MS;Kim, HS
基质金属蛋白酶-9（MMP-9）的异常表达与恶性肿瘤的侵袭和血管生成过程以及中枢神经系统的炎性疾病有关。因此，需要开发能够抑制或抑制MMP-9的化合物来治疗脑肿瘤。我们研究了人参皂苷代谢物化合物K（20-O-（beta-D-glucopyranosyl）-20（S）-protopanaxadiol）对人星形胶质瘤细胞MMP-9表达的影响。化合物K显著抑制PMA诱导的MMP-9的分泌和蛋白表达。化合物K对MMP-9表达的抑制作用与MMP-9 mRNA水平的降低和MMP-9启动子活性的抑制相关。化合物K介导的MMP-9基因表达的抑制似乎是通过AP-1发生的，因为其DNA结合和转录活性被药剂抑制。此外，化合物K显著抑制PMA介导的p38 MAPK、ERK和JNK的活化，这些是AP-1的上游调节剂。最后，化合物K抑制胶质瘤细胞的体外侵袭性。因此，化合物K抑制MMP-9表达可能具有控制脑肿瘤生长和侵袭性的治疗潜力。(c)2005 Wiley-Liss，Inc.
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-(beta-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. (c) 2005 Wiley-Liss, Inc.