Abstract
In the present study we evaluated the anti-angiogenic activities of β-escin (the major active compound of Aesculus hippocastanum L. seeds). Human umbilical-vein endothelial cells (HUVECs) were used as an in vitro model for studying the molecular mechanism underlying the anti-angiogenic effect of β-escin. We investigated the in vitro effects on proliferation, migration, and tube formation of HUVECs and in vivo anti-angiogenic activity was evaluated in a chick chorioallantoic membrane (CAM) angiogenesis assay. Moreover, the effect on gene expressions was determined by the RT2 ProfilerTM human angiogenesis PCR Array. It was found that β-escin exerts inhibitory effect on the basic fibroblast growth factor (bFGF)-induced proliferation, migration and tube formation, as well as CAM angiogenesis in vivo. The inhibition of critical steps of angiogenic process observed with β-escin could be partially explained by suppression of Akt activation in response to bFGF. Moreover, the anti-angiogenic effects of β-escin could also be mediated via inhibition of EFNB2 and FGF-1 gene expressions in endothelial cells. In conclusion, β-escin affects endothelial cells as a negative mediator of angiogenesis in vitro and in vivo and may therefore be considered as a promising candidate for further research elucidating its underlying mechanism of action.
Highlights
Mounting evidence has demonstrated that tumor growth and progression depend on tumor angiogenesis
We showed that β-escin could modulate in vitro Human umbilical-vein endothelial cells (HUVECs) plant-based β-escin both on HUVECs and using chorioallantoic membrane (CAM) assay
In order to determine whether such activity would be applicable to a clinical cancer setting, we investigated the ability of β-escin, to inhibit angiogenesis in vivo
Summary
Mounting evidence has demonstrated that tumor growth and progression depend on tumor angiogenesis. Considering the importance of vascular growth in tumor progression, the inhibition of angiogenesis has been explored as therapeutic prospect to treat cancer [2]. Several anti-angiogenic agents have been developed to inhibit different stages of angiogenesis in tumor growth processes. In this context, the monoclonal antibody designed against vascular endothelial growth factor-A (VEGF-A) (bevacizumab) was the first US Food and. To VEGF, anti-angiogenic strategies have focused on blocking the angiogenesis by selective small molecule tyrosine kinase inhibitors (TKIs) and FDA has approved over 19 oral TKIs for the treatment of malignancies in hematology/oncology [5]
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