Green tea polyphenol (-)-epigallocatechin 3-gallate inhibits MMP-2 secretion and MT1-MMP-driven migration in glioblastoma cells

被引:137
作者
Annabi, B
Lachambre, MP
Bousquet-Gagnon, N
Pagé, M
Gingras, D
Béliveau, R
机构
[1] Hop St Justine, Ctr Rech, Mol Med Lab, Montreal, PQ H3T 1C5, Canada
[2] Univ Quebec, Montreal, PQ H3C 3P8, Canada
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2002年 / 1542卷 / 1-3期
基金
英国医学研究理事会;
关键词
angiogenesis; cancer; glioblastoma; green tea; membrane-type 1 matrix metalloproteinase;
D O I
10.1016/S0167-4889(01)00187-2
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We have recently shown that green tea polyphenols, and especially (-)-epigallocatechin 3-gallate (EGCg), acted as potent inhibitors of matrix metalloproteinase activities as well as of proMMP-2 activation (M. Demeule, M. Brossard, M. Page, D. Gingras, R. Beliveau, Biochim. Biophys. Acta 1478 (2000)). In the present work, we sought to examine the involvement of MT1-MMP in the EGCg-induced inhibition of proMMP-2 activation. The incubation of U-87 glioblastoma cells in the presence of concanavalin A or cytochalasin D, two potent activators of MT1-MMP, resulted in proMMP-2 activation that was correlated with the cell surface proteolytic processing of MT1-MMP to its inactive 43 kDa form. Addition of EGCg strongly inhibited the MT1-MMP-dependent proMMP-2 activation. The inhibitory effect of EGCg on MT1-MMP was also demonstrated by the down-regulation of MT1-MMP transcript levels and by the inhibition of MT1-MMP-driven cell migration of transfected COS-7 cells. These observations suggest that this catechin may act at both the MT1-MMP gene and protein expression levels. In addition, treatment of cells with non-cytotoxic doses of EGCg significantly reduced the amount of secreted proMMP-2, and led to a concomitant increase in intracellular levels of that protein. This effect was similar to that observed using well-characterized secretion inhibitors such as brefeldin A and manumycin, suggesting that EGCg could also potentially act on intracellular secretory pathways. Taken together, these results indicate that EGCg targets multiple MMP-mediated cellular events in cancer cells and provides a new mechanism for the anticancer properties of that molecule. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:209 / 220
页数:12
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