: Several cohort studies have reported that green tea extract has potential as a natural anti-tumor medicine. Catechins found in green tea, especially -epigallocatechin-3-gallate EGCG , are thought to be responsible for most of the anti-tumor activity. In a previous study, a green tea extract inhibited matrix metalloprotease MMP activity produced by Langerhans-like cells ELD-1 to a greater extent than an equivalent amount of EGCG alone, suggesting that other factors might be involved in the inhibition of MMP and angiogenesis. Green tea contains not only EGCG but also various compounds such as theanine, caffeine, sugars and other polyphenols. We hypothesized that one of the other factors involved in MMP inhibition might be theanine. In the present study, we investigated the effects of theanine and EGCG on MMPs using cultured ELD-1 cells. ELD-1 cells treated with theanine did not show decreased MMP-9 mRNA levels but resulted in increased levels of tissue inhibitors of metalloproteinase-1 TIMP-1 mRNA. To investigate tube formation in vitro, an angiogenesis assay kit of co-cultured human umbilical vein endothelial cells HUVEC with fibroblasts was employed. Macroscopically, tube formation with theanine and/or EGCG treatment was detected and an additive inhibitory effect of theanine and EGCG was observed. Our results demonstrated that the additive effect of theanine and EGCG from tea extract on tube formation occurred via MMP-9 and TIMP-1. This may be one of the reasons why green tea has potential as an anti-tumor natural medicine.
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