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

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 anti-proliferation, -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.