Antiangiogenic Activity of Xanthomicrol and Calycopterin, Two Polymethoxylated Hydroxyflavones in Both In Vitro and Ex Vivo Models

被引:27
作者
Abbaszadeh, Hassan [1 ]
Ebrahimi, Soltan Ahmad [1 ]
Akhavan, Maziar Mohammad [2 ]
机构
[1] Iran Univ Med Sci, Dept Pharmacol, Sch Med, Tehran, Iran
[2] Shahid Beheshti Univ Med Sci, Skin Res Ctr, Lab Prot & Enzyme, Tehran, Iran
关键词
xanthomicrol; calycopterin; antiangiogenic activity; rat aortic ring assay; endothelial tube formation assay; VEGF; TUMOR ANGIOGENESIS; CANCER; FLAVONOIDS;
D O I
10.1002/ptr.5179
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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 mu g/mL, and calycopterin suppressed microvessel outgrowth by 89% at 5 mu g/mL. Suramin and thalidomide, used at 20 mu g/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 mu g/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 mu g/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. Copyright (c) 2014 John Wiley & Sons, Ltd.
引用
收藏
页码:1661 / 1670
页数:10
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