Crocetin Inhibits Invasiveness of MDA-MB-231 Breast Cancer Cells via Downregulation of Matrix Metalloproteinases
Crocetin Inhibits Invasiveness of MDA-MB-231 Breast Cancer Cells via Downregulation of Matrix Metalloproteinases
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DOI：
10.1055/s-0030-1250178
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发表时间：
2011-01-01
期刊：
影响因子：
2.7
通讯作者：
Lamari, Fotini N.
中科院分区：
文献类型：
--
作者：
Chryssanthi, Dimitra G.;Dedes, Petros G.;Lamari, Fotini N.
藏红花酸是一种类胡萝卜素二羧酸，其在自然界中与葡萄糖或龙胆二糖单元酯化形成藏红花素，藏红花素是藏红花（一种具有许多药用用途的香料）的丰富组分。我们以前曾报道过，西红花苷，西红花酸抑制乳腺癌细胞增殖。为了进一步研究西红花酸对乳腺癌细胞的作用，我们使用了高度侵袭性的MDA-MB-231细胞，并用WST-1测定法测量了细胞的存活率，并通过重建的基底膜测量了细胞的侵袭力。孵育24小时后，西红花酸在1和10 μ M浓度下不仅显著抑制增殖，而且显著抑制侵袭。肿瘤的侵袭和转移与基质金属蛋白酶（MMPs）的表达有关。为了研究可能伴随所观察到的西红花酸效应的MMP表达的分子变化，通过RT-PCR研究了MMP的基因表达，而蛋白质表达和明胶分解活性分别用Western印迹和酶谱法测定。西红花酸和全反式维甲酸（ATRA）均能显著抑制pro-MT 1-MMP和pro-MT 2-MMP的基因和蛋白表达。在无血清条件下与10 μ M西红花酸孵育24小时可降低pro-MMP-9活性和pro-MMP-2/MMP-2蛋白水平。当培养基中培养血清2和5%，藏红花酸在10 μ M也降低明胶酶活性。上述结果表明，西红花酸的主要代谢产物西红花酸通过下调MMP表达来抑制MDA-MB-231细胞的侵袭力。
Crocetin is a carotenoid dicarboxylic acid which, in nature, is esterified with glucose or gentiobiose units forming the crocins, abundant components of saffron (a spice with many reputed medicinal uses). We have previously reported that saffron, crocins and crocetin inhibit breast cancer cell proliferation. In order to further study the effect of crocetin on breast cancer cells, we used the highly invasive MDA-MB-231 cells and measured the viability with the WST-1 assay and the invasiveness through a reconstituted basement membrane. After 24 h incubation, crocetin significantly inhibited not only proliferation but also invasion at 1 and 10 mu M. Cancer invasiveness and metastasis are associated with the expression of matrix metalloproteinases (MMPs). In order to study the molecular changes of MMP expression that might accompany the observed crocetin effects, gene expression of MMPs was studied by RT-PCR, whereas protein expression and gelatinolytic activity were determined with Western blotting and zymography, respectively. The gene and protein expression of pro-MT1-MMP and pro-MT2-MMP were greatly attenuated by both crocetin and all-trans-retinoic acid (ATRA, used as control). Incubation with 10 mu M crocetin for 24 h in serum-free conditions reduced pro-MMP-9 activity and pro-MMP-2/MMP-2 protein levels. When cultured in media with sera 2 and 5%, crocetin at 10 mu M also reduced gelatinase activity. The above findings show that crocetin, the main metabolite of crocins, inhibits MDA-MB-231 cell invasiveness via downregulation of MMP expression.