In vitro Anti-angiogenic Activity of Persian Shallot (Allium Hirtifolium) Extract Is Mediated Through Inhibition of Endothelial Cell Proliferation/Migration and Down-regulation of VEGF and MMP Expression

authors:

avatar Delnia Arshadi 1 , avatar Kamran Mansouri 2 , avatar Reza Khodarahmi 2 , avatar Parivash Seyfi 1 , avatar Yadollah Shakiba 2 , avatar Ali Mostafaei 2 , *

Faculty of Pharmaceutical Sciences, Kermanshah University of Medical Sciences, Kermanshah, Iran
Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

How To Cite Arshadi D, Mansouri K, Khodarahmi R, Seyfi P, Shakiba Y, et al. In vitro Anti-angiogenic Activity of Persian Shallot (Allium Hirtifolium) Extract Is Mediated Through Inhibition of Endothelial Cell Proliferation/Migration and Down-regulation of VEGF and MMP Expression. J Rep Pharm Sci. 2014;3(1):e147728. 

Abstract

Development of phytotherapies aimed at angiogenesis inhibition, in combination with classical anti-cancer therapies, is among the most intensively studied approaches for treatment of cancer. Epidemiological and animal studies have indicated that consumption of Allium species like shallot is associated with a reduced risk of cancer development. As a continuation of our efforts to study and characterize the effective anti-angiogenic agents from Allium species, here, we investigated the effects of aqueous extract of shallot on critical steps and mediators of in vitro angiogenesis. The antiproliferation, -migration, and -tubulogenesis properties of the aqueous extract of shallot (at 100 - 1500 μg/ml) were evaluated using three-dimensional capillary tube formation as well as a wound-healing assay in endothelial cell-based experimental systems. In addition, the effect of the extract on vascular endothelial growth factor (VEGF) secretion and matrix metalloproteinase (MMP-2 and -9) expression was assayed using ELISA, gelatin zymography, and RT-PCR techniques. Treatment with the aqueous extract of shallot at ≥ 500 μg/ml concentrations resulted in significant decreases in endothelial cell proliferation, migration, and tubulogenesis. Moreover, the extract caused a dose-related inhibition of VEGF secretion and MMP-2/-9 expression. Taking all the data into account, the current study indicated that shallot – containing potent anti-angiogenic properties - exerts its inhibitory effect mainly through down-regulation of VEGF and MMP-2/-9; essential angiogenic mediators in many malignant and chronic inflammatory diseases.