Lee Syng-Ook, Jeong Yun-Jeong, Kim Mihyun, Kim Cheorl-Ho, Lee In-Seon
Department of Food Science and Technology, The Center for Traditional Microorganism Resources (TMR), Keimyung University, 1000 Sindang-Dong, Dalseo-Gu, Daegu 704-701, Republic of Korea.
Biochem Biophys Res Commun. 2008 Feb 22;366(4):1019-24. doi: 10.1016/j.bbrc.2007.12.068. Epub 2007 Dec 26.
Matrix metalloproteinase-9 (MMP-9) plays an important role in the invasion and metastasis of cancer cells. In this study, we examined the inhibitory effect of capillarisin, a bioactive flavonoid of Artemisia capillaries, on phorbol myristate acetate (PMA)-induced MMP-9 expression in MCF-7 human breast carcinoma cells. Capillarisin significantly and selectively suppressed PMA-induced MMP-9 expression in MCF-7 and the Matrigel invasion assay showed that capillarisin reduces PMA-induced invasion of MCF-7 cells. Capillarisin has been found to suppress PMA-induced MMP-9 expression through inhibition of the NF-kappaB-dependent transcriptional activity of MMP-9 gene via p38 MAPK and JNK signaling pathways. However, capillarisin had no effect on enzymatic activity of MMP-9 and expression of tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2, the major endogenous inhibitors of MMPs. These results suggest that capillarisin represents a potential anti-metastatic agent suppressing cancer cell invasion through specific inhibition of NF-kappaB-dependent MMP-9 gene expression.
基质金属蛋白酶-9（MMP-9）在癌细胞的侵袭和转移中起重要作用。在本研究中，我们检测了茵陈色原酮（一种茵陈蒿的生物活性黄酮类化合物）对佛波酯（PMA）诱导的MCF-7人乳腺癌细胞中MMP-9表达的抑制作用。茵陈色原酮显著且选择性地抑制了PMA诱导的MCF-7细胞中MMP-9的表达，并且基质胶侵袭实验表明茵陈色原酮减少了PMA诱导的MCF-7细胞侵袭。已发现茵陈色原酮通过p38丝裂原活化蛋白激酶（MAPK）和应激活化蛋白激酶（JNK）信号通路抑制MMP-9基因的核因子κB（NF-κB）依赖性转录活性，从而抑制PMA诱导的MMP-9表达。然而，茵陈色原酮对MMP-9的酶活性以及基质金属蛋白酶组织抑制剂（TIMP）-1和TIMP-2（MMPs的主要内源性抑制剂）的表达没有影响。这些结果表明，茵陈色原酮是一种潜在的抗转移剂，通过特异性抑制NF-κB依赖性MMP-9基因表达来抑制癌细胞侵袭。
