Kawabata Kyuichi, Murakami Akira, Ohigashi Hajime
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Japan.
Biosci Biotechnol Biochem. 2005 Feb;69(2):307-14. doi: 10.1271/bbb.69.307.
Overexpression of matrix metalloproteinases (MMPs) is associated with cancer metastasis. We assessed mRNA expression of MMPs in six human colorectal cancer cell lines and found a considerable level of MMP-7 expression in HT-29 cells. Next, we searched for natural and synthetic compounds that cause a reduction in the production of proMMP-7 protein, and found that nobiletin (NOB), quercetin, valeryl salicylate, and sulindac sulfone demonstrated marked inhibition. Importantly, NOB attenuated proMMP-7 protein and its mRNA expression both concentration- and time-dependently via a reduction of activator protein-1 (AP-1) DNA binding activity, suggesting it as a promising agent for suppression of cancer cell invasion and metastasis through MMP-7 gene repression.
基质金属蛋白酶（MMPs）的过表达与癌症转移有关。我们评估了六种人结肠癌细胞系中MMPs的mRNA表达，发现在HT-29细胞中MMP-7表达水平相当高。接下来，我们寻找可降低前MMP-7蛋白产生的天然和合成化合物，发现川陈皮素（NOB）、槲皮素、戊酰水杨酸酯和舒林酸砜表现出显著抑制作用。重要的是，NOB通过降低激活蛋白-1（AP-1）的DNA结合活性，浓度和时间依赖性地减弱前MMP-7蛋白及其mRNA表达，表明它是一种通过抑制MMP-7基因来抑制癌细胞侵袭和转移的有前景的药物。
