Inhibition of vascular endothelial growth factor-induced angiogenesis by chlorogenic acid via targeting the vascular endothelial growth factor receptor 2-mediated signaling pathway

Abstract

This study aimed at delineating the mechanism of the anti-angiogenic effect of chlorogenic acid. Chlorogenic acid demonstrated significant inhibitory effects on vascular endothelial growth factor (VEGF)-induced proliferation, migration, invasion and tube formation in human umbilical vein endothelial cells (HUVECs) while the quantitative endogenous alkaline phosphatase assay and microscopic observation on zebrafish embryo model further confirmed its anti-angiogenic property. In addition, treatment of HUVECs with chlorogenic acid significantly decreased expression of angiogenic markers including angiopoietin-2, matrix metalloproteinase-2 and focal adhesion kinase. Proteomic profile analysis also revealed chlorogenic acid treatment reduced the multi-target expression including endoglin, endothelin-1 and interleukin-8 in HUVECs. The underlying mechanism may involve the reactive oxygen species scavenging activity of chlorogenic acid, which further attenuates the VEGFR2-mediated signaling and consequent phosphorylation of VEGFR2, extracellular signal regulated kinase 1/2 and serine-threonine kinase.

Keywords

• Angiogenesis
• Chlorogenic acid
• HUVECs
• VEGF
• Zebrafish