Role of the estrogen antagonist ICI 182,780 in vessel assembly and apoptosis of endothelial cells.

Angiogenesis is required during tumor progression. Emerging data, including the presence of estrogen receptors in endothelium, suggests that estrogens can mediate endothelial proliferation and differentiation. Therefore, it is likely that anti-estrogenic drugs can also exert their effects in endothelial cells. The purpose of this work was to evaluate the effect of one anti-estrogenic agent, ICI 182,780, in human umbilical vein endothelial cells (HUVECs). Treatment of HUVECs with 5 different concentrations of ICI 182,780 resulted in decreased cell viability and increase in apoptosis. Gene expression profile of these ICI-treated cells evaluated by cDNA array presented an upregulation of 68 newly expressed genes, whose expression was absent from both control and 17beta-estradiol-treated HUVECs. Most of these genes were implicated in both intrinsic and extrinsic apoptotic pathways. Furthermore, ICI 182,780 incubation prevented HUVECs from formity capillary-like tubules in a Matrigel assay. These findings suggest that besides blocking tumor cell proliferation in an estrogen receptor-dependent manner, ICI 182,780 impaired angiogenesis by preventing branching and capillary-like tubule formation and by activating apoptotic pathways in endothelial cells.