title: Antiangiogenic activity of xanthomicrol and calycopterin, two polymethoxylated hydroxyflavones in both in vitro and ex vivo models.
abstract: Our previous studies had shown xanthomicrol and calycopterin, two plant-derived flavonoids, to have selective antiproliferative activity against some malignant cell lines. The present study is focused on the investigation of antiangiogenic potential of these two flavonoids, using in vitro and ex vivo models. Xanthomicrol and calycopterin were found to have potent inhibitory effects on microvessel outgrowth in the rat aortic ring assay. Xanthomicrol was able to completely block microvessel sprouting at 10 µg/mL, and calycopterin suppressed microvessel outgrowth by 89% at 5 µg/mL. Suramin and thalidomide, used at 20 µg/mL as positive controls, inhibited microvessel formation by 23% and 64%, respectively. The flavones also inhibited endothelial cell tube formation and human umbilical vein endothelial cell proliferation at 0.5, 5, and 10 µg/mL. In order to delineate the underlying mechanisms of antiangiogenic activity of these flavones, we investigated the influences of xanthomicrol and calycopterin on expression of vascular endothelial growth factor (VEGF) and basic-fibroblast growth factor (b-FGF) in endothelial cells. These flavones were able to inhibit VEGF expression at 0.5, 5, and 10 µg/mL, but they had little or no effect on b-FGF expression. These findings suggest that xanthomicrol and calycopterin possess potent antiangiogenic activities, which may be due to their inhibitory influences on VEGF expression.
authors.affiliation: Iran University of Medical Sciences, School of Medicine, Department of Pharmacology, Tehran, Iran.
authors.forename: Hassan
authors.initials: H
authors.lastname: Abbaszadeh
authors.forename: Soltan Ahmad
authors.initials: SA
authors.lastname: Ebrahimi
authors.forename: Maziar Mohammad
authors.initials: MM
authors.lastname: Akhavan
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D047309:Flavones / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D019686:Lamiaceae / Q000737:chemistry; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D047309:Flavones; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C462036:xanthomicrol; C533734:calycopterin
keywords: VEGF; antiangiogenic activity; calycopterin; endothelial tube formation assay; rat aortic ring assay; xanthomicrol