Melatonina como modulador de la expresión de angiopoyetinas en células HUVEC Y MCF-­7

Abstract

Melatonin exerts oncostatic actions on human breast cancer cells. Angiopoietins are cytokines that regulate angiogenesis and the angiopoietin/tie system is a vascular specific ligand/receptor system that play a critical role in endothelial cell differentiation and blood vessel morphogenesis by regulating angiogenic-remodeling processes such as vessel stabilization/destabilization and pericyte recruitment or loss. Since it is known that melatonin has antiangiogenic actions, the aim of the present study was to investigate the regulatory effects of melatonin on angiopoietins 1 and 2 expression and Tie receptor in endothelial and human breast cancer cells. To accomplish this, we cocultured human breast cancer cells (MCF-7) with human umbilical vein endothelial cells (HUVECs). Melatonin increased Ang1 and Ang2 mRNA expression in MCF-7 cells and HUVEC at physiological and pharmacological concentrations. When HUVEC were incubated without the presence of MCF-7 both concentrations increased the Tie2 expression. However, the Tie2 expression in coculture was stimulated by melatonin only at 10-9 M. Since it is known that melatonin inhibits VEGF expression in MCF-7 cells and that an increase in angiopoietins expression in the absence of VEGF lead to vessel regression, our findings suggest the melatonin could inhibit angiogenesis through an up-regulation on angiopoietins expression and a downregulation on VEGF expression.