Tempe (fermented soybeans) isoflavonoids and Tempe extract downregulate the angiogenesis and invasion-related stromal Etsl transcription factor in cultured human endothelial cells and fibroblasts

摘要

Tempe is a popular food in south east asia (Tempe kedele) formed by fermentation of soybeans with rhizopus oligosporus. It contains several isoflavones such as the tyrosine kinase inhibitor Genistein. Genistein and some other isoflavones have been shown to inhibit basic fibroblast growth factor (bFGF) induced endothelial cell (EC) proliferation, which is an important step during tumor vascularization. The most important angiogenic factor in tumors is vascular endothelial cell growth factor (VEGF), which, like bFGF, acts on ECs through tyrosine-kinase receptors (Flt I and KDR). Here we show, that various isoflavones and Tempe raw extract inhibit within cultured human umbilical vein endothelial cells (HUVECs) the VEGF-induced expression of the Ets 1 transcription factor, which is strongly implicated in new blood vessel formation under both physiological and pathological conditions. Ets 1 expression is also reduced by certain isoflavones after bFGF induction in cultured human fibroblasts. In tumors stromal fibroblasts are known to promote tumor invasion by the secretion of different matrix-degrading proteases and Ets 1 is strongly supposed to be involved in the transcriptional regulation of their activity. Tempe constituents could become valuable tools for the newly emerging cancer therapy aimed at the tumor stroma by inhibiting both angiogenesis and tumor invasion.