Grape seed proanthocyanidins inhibit angiogenesis via the downregulation of both vascular endothelial growth factor and angiopoietin signaling

doi:10.1016/j.nutres.2012.05.012

	Grape seed proanthocyanidins inhibit angiogenesis via the downregulation of both vascular endothelial growth factor and angiopoietin signaling
	Huang, Shuangsheng 1; Yang, Ninggang 2; Liu, Yuanyuan3 ; Hu, Lamei 4; Zhao, Jin 1; Gao, Jing 1; Li, Yongquan 1; Li, Caili 1; Zhang, Xiaosu 1; Huang, Tao 1
刊名	NUTRITION RESEARCH
	2012-07-01
卷号	32 页码:530-536
关键词	Grape Seed Proanthocyanidins Angiogenesis Vegfr2 Tie2 Hmec-1 Endothelial Cells Chick Chorioallantoic Membrane
ISSN号	0271-5317
DOI	10.1016/j.nutres.2012.05.012
文献子类	Article
英文摘要	Vascular endothelial growth factor (VEGF)/VEGF receptor 2 and angiopoietin 1/tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 signaling pathways regulate different, but complementary, aspects of blood vessel growth in tumors. Simultaneous inhibition of both pathways not only exhibits additive antiangiogenic effects but also overcomes the resistance to anti-VEGF therapy. Grape seed proanthocyanidins (GSPs) are widely consumed dietary supplements with antiangiogenic activity. However, the molecular mechanisms underlying their antiangiogenic action have not been fully understood. We hypothesized that GSPs modulate multiple signaling pathways to exhibit antiangiogenic effects. In the present study, we aimed to test this hypothesis by examining the effects of GSPs on human microvascular endothelial cell-1 and chick chorioallantoic membrane. Our results showed that GSPs inhibited the migration, matrix metalloproteinase-2 and -9 secretion, and tube formation of human microvascular endothelial cell-1 in vitro in a dose-dependent manner. In addition, chick chorioallantoic membrane angiogenesis assay showed that GSPs inhibited neovascularization in a dose-dependent manner. Furthermore, we demonstrated that GSPs inhibited the phosphorylation of VEGF receptor 2 and tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 as well as downstream signaling component extracellular signal-regulated kinase 1/2. In summary, these data suggest that GSPs inhibit both VEGF and angiopoietin 1 signaling to execute the antiangiogenic effects and indicate that GSPs could be developed as a pharmacologically safe chemopreventive agent against cancer. (C) 2012 Elsevier Inc. All rights reserved.
资助项目	Scientific Research Innovation Team of Northwest University for Nationalities[XBMUCXTD-2011-1]
WOS关键词	TUMOR-GROWTH ; CANCER ; CELLS ; VEGF ; EXTRACT ; KINASE
WOS研究方向	Nutrition & Dietetics
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000307917100008
内容类型	期刊论文
源URL	[http://119.78.100.186/handle/113462/49031]
专题	中国科学院近代物理研究所
通讯作者	Huang, Shuangsheng
作者单位	1.NW Univ Nationalities, Coll Med, Lanzhou 730030, Peoples R China 2.Lanzhou First Peoples Hosp, Dept Urol, Lanzhou 730030, Peoples R China 3.Chinese Acad Sci, Inst Modern Phys, Lanzhou 730000, Peoples R China 4.Lanzhou Univ, Sch Basic Med Sci, Inst Pharmacol, Lanzhou 730000, Peoples R China
推荐引用方式 GB/T 7714	Huang, Shuangsheng,Yang, Ninggang,Liu, Yuanyuan,et al. Grape seed proanthocyanidins inhibit angiogenesis via the downregulation of both vascular endothelial growth factor and angiopoietin signaling[J]. NUTRITION RESEARCH,2012,32:530-536.
APA	Huang, Shuangsheng.,Yang, Ninggang.,Liu, Yuanyuan.,Hu, Lamei.,Zhao, Jin.,...&Huang, Tao.(2012).Grape seed proanthocyanidins inhibit angiogenesis via the downregulation of both vascular endothelial growth factor and angiopoietin signaling.NUTRITION RESEARCH,32,530-536.
MLA	Huang, Shuangsheng,et al."Grape seed proanthocyanidins inhibit angiogenesis via the downregulation of both vascular endothelial growth factor and angiopoietin signaling".NUTRITION RESEARCH 32(2012):530-536.