College of Natural Resources and Life Science, BK21 Center for Silver-Bio Industrialization, Dong-A University, Busan 604-714, Republic of Korea.
Biochem Biophys Res Commun. 2012 May 4;421(2):190-6. doi: 10.1016/j.bbrc.2012.03.133. Epub 2012 Apr 4.
The expression of matrix metalloproteinase (MMPs)-9 is critical for cell migration and can lead to invasion and metastasis of cancer cells. In the present study, we examined the inhibitory effects of JNP3, a new compound which was isolated from traditional Chinese medicine, on cell invasion and MMP-9 activation in phorbol myristate acetate (PMA)-induced MCF-7 cells. Treatment with JNP3 significantly and selectively inhibited PMA-induced MMP-9 secretion, mRNA expression and protein levels, and these results led to reduction of cell invasion and migration in PMA-induced MCF-7 cells. The results of MMP-9 promoter assay and EMSA showed that JNP3 specifically inhibited PMA-induced MMP-9 gene expression by blocking NF-κB-dependent transcriptional activity. In addition, PMA-induced phosphorylation of ERK1/2 and JNK were suppressed by JNP3 treatment, whereas the phosphorylation of p38 MAPK was not affected by JNP3. These results suggest that JNP3 can be potential anti-cancer agents through specific inhibition of NF-κB-dependent MMP-9 gene expression.
基质金属蛋白酶（MMPs）-9 的表达对于细胞迁移至关重要，并且可能导致癌细胞的侵袭和转移。在本研究中，我们研究了 JNP3 的抑制作用，JNP3 是从中药中分离出来的一种新化合物，研究其对佛波酯（PMA）诱导的 MCF-7 细胞中细胞侵袭和 MMP-9 激活的抑制作用。JNP3 处理显著且选择性地抑制 PMA 诱导的 MMP-9 分泌、mRNA 表达和蛋白水平，这些结果导致 PMA 诱导的 MCF-7 细胞中细胞侵袭和迁移减少。MMP-9 启动子分析和 EMSA 结果表明，JNP3 通过阻断 NF-κB 依赖性转录活性特异性抑制 PMA 诱导的 MMP-9 基因表达。此外，JNP3 处理抑制了 PMA 诱导的 ERK1/2 和 JNK 的磷酸化，而 JNP3 不影响 p38 MAPK 的磷酸化。这些结果表明，JNP3 通过特异性抑制 NF-κB 依赖性 MMP-9 基因表达，可能成为潜在的抗癌药物。
