Dell'Aica Isabella, Donà Massimo, Sartor Luigi, Pezzato Elga, Garbisa Spiridione
Department of Experimental Biomedical Sciences, Medical School of Padova, Padova, Italy.
Lab Invest. 2002 Dec;82(12):1685-93. doi: 10.1097/01.lab.0000043122.00384.91.
Consumption of green tea has been associated with prevention of cancer development, metastasis, and angiogenesis. Given the crucial role of the matrix metallo-proteinase-2 (MMP-2) on the degradation of the extracellular matrix instrumental to invasion, we examined the effect of the main flavanol present, (-)epigallocatechin-3-gallate (EGCG), on membrane-type 1 MMP (MT1-MMP), the receptor/activator of MMP-2. In-solution fluorimetric assay with activated MT1-MMP and gelatin-zymography with MT1-MMP catalytic domain alone and pro-MMP-2 activation by the same domain revealed dose-dependent inhibition of MT1-MMP at EGCG concentrations slightly lower than that reported to inhibit MMP-2 and MMP-9. Cytofluorimetry and immunolocalization revealed that EGCG does not impair MT1-MMP/TIMP-2/MMP-2 presence on the cell membrane. In the membrane extract of HT-1080 human fibrosarcoma cells, 10 micro M EGCG caused a strong increase in MT1-MMP level and accumulation of pro-MMP-2 while leaving activated MMP-2 unchanged. EGCG thus exerts inhibition of MT1-MMP, which restrains activation of MMP-2; this may confer the antiangiogenic and antimetastatic activity associated with green tea.
饮用绿茶与预防癌症发展、转移和血管生成有关。鉴于基质金属蛋白酶-2（MMP-2）在促进侵袭的细胞外基质降解中起关键作用，我们研究了绿茶中主要的黄烷醇（-）表没食子儿茶素-3-没食子酸酯（EGCG）对膜型1基质金属蛋白酶（MT1-MMP）的影响，MT1-MMP是MMP-2的受体/激活剂。使用活化的MT1-MMP进行溶液荧光测定，以及单独使用MT1-MMP催化结构域进行明胶酶谱分析，并通过同一结构域激活前MMP-2，结果显示在EGCG浓度略低于据报道可抑制MMP-2和MMP-9的浓度时，MT1-MMP受到剂量依赖性抑制。细胞荧光分析和免疫定位显示，EGCG不会损害MT1-MMP/TIMP-2/MMP-2在细胞膜上的存在。在HT-1080人纤维肉瘤细胞的膜提取物中，10微摩尔EGCG导致MT1-MMP水平显著升高和前MMP-2积累，而活化的MMP-2保持不变。因此，EGCG可抑制MT1-MMP，从而抑制MMP-2的激活；这可能赋予了绿茶相关的抗血管生成和抗转移活性。
