Effect of EGCG, a major component of green tea, on the expression of Ets-1, c-Fos, and c-Jun during angiogenesis in vitro

In this study, we used rat aortic endothelial cells and human umbilical vein endothelial cells growing in collagen gel as a model system to study the tea catechin, (−)-epigallocatechin (EGCG), on the differential expression of transcription factors, Ets-1, c-Fos, and c-Jun during endothelial morphogenesis in vitro. Cells growing in collagen gel from 0 to 2 h remained spherical. After 6 h, the cells became elongated and underwent morphogenesis. At 24 h, cells started to organize to form capillary-like tubular structures. At 48 h, most cells in the gel formed a network of branching and tubular structures. Immunohistochemistry and immunofluorescence microscopy showed that the reaction products of Ets-1, c-Fos, and c-Jun presented predominantly in the nucleus. No reaction products appeared in the cells that were organized to form capillary-like tubular structures. After adding EGCG to the collagen gel, cells became elongated in the first 6 h and then remained quiescent. No tubular structure was formed. Western blotting showed that the levels of Ets-1, c-Fos, and c-Jun reached the highest levels at 12–24 h, decreasing to the basal level at 48 h. After adding EGCG to the collagen gel, levels were lower than for the non-EGCG-treated groups. These results indicated that the morphogenesis of endothelial cells in collagen gel was inhibited by EGCG through the down-regulation of Ets-1, c-Fos, and c-Jun.