LYG-202, a Newly Synthesized Flavonoid, Exhibits Potent Anti-angiogenic Activity In Vitro and In Vivo

被引：21
作者：
Chen, Yan [1 ]
Lu, Na [1 ]
Ling, Yun [1 ]
Wang, Ling [1 ]
You, Qidong [1 ]
Li, Zhiyu [1 ]
Guo, Qinglong [1 ]
机构：
[1] China Pharmaceut Univ, Jiangsu Key Lab Carcinogenesis & Intervent, Nanjing 210009, Peoples R China
来源：
JOURNAL OF PHARMACOLOGICAL SCIENCES | 2010年 / 112卷 / 01期
基金：
中国国家自然科学基金;
关键词：
flavonoid; angiogenesis; human umbilical vein endothelial cell (HUVEC); vascular endothelial growth factor (VEGF); KDR/Flk-1 (VEGFR-2); ENDOTHELIAL GROWTH-FACTOR; INDUCED TYROSINE PHOSPHORYLATION; SIGNALING PATHWAYS; VEGF; INHIBITION; MECHANISMS; KDR/FLK-1; RECEPTOR;
D O I：
10.1254/jphs.09213FP
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
LYG-202 (C25H30N2O5) is a newly synthesized flavonoid that has been confirmed to possess an antitumor effect, but the mechanism is unclear. Our present study was performed to identify the anti-angiogenic activity of this novel compound in vitro and in vivo. LYG-202 inhibited vascular endothelial growth factor (VEGF) Stimulated migration and tube formation of human umbilical vein endothelial cells and arrested microvessel outgrowth from rat aortic rings in vitro. Meanwhile, LYG-202 suppressed the neovascularization of Chicken Chorioallantoic Membrane in vivo. Mechanistic studies revealed that LYG-202 suppressed the VEGF-induced tyrosine phosphorylation of KDR/Flk-1 (VEGFR-2) as well as its downstream protein kinases activation, by decreasing phosphorylated forms of serine/threonine kinase Akt, extracellular signal-regulated kinase, and p38 mitogen-activated protein kinase. LYG-202 exerts anti-angiogenic activity both in vitro and in vivo, and these results suggest that it deserves further investigation as a promising anti-tumor angiogenesis compound.
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收藏
页码：37 / 45
页数：9
相关论文
共 38 条
  • [11] Transgenic mouse models of tumour angiogenesis: The angiogenic switch, its molecular controls, and prospects for preclinical therapeutic models
    Hanahan, D
    Christofori, G
    Naik, P
    Arbeit, J
    [J]. EUROPEAN JOURNAL OF CANCER, 1996, 32A (14) : 2386 - 2393
  • [12] The biochemistry and medical significance of the flavonoids
    Havsteen, BH
    [J]. PHARMACOLOGY & THERAPEUTICS, 2002, 96 (2-3) : 67 - 202
  • [13] Inhibition of MAPK kinase signaling pathways suppressed renal cell carcinoma growth and angiogenesis in vivo
    Huang, Dan
    Ding, Yan
    Luo, Wang-Mei
    Bender, Stephanie
    Qian, Chao-Nan
    Kort, Eric
    Zhang, Zhong-Fa
    VandenBeldt, Kristin
    Duesbery, Nicholas S.
    Resau, James H.
    Teh, Bin Tean
    [J]. CANCER RESEARCH, 2008, 68 (01) : 81 - 88
  • [14] p38 MAP kinase -: a molecular switch between VEGF-induced angiogenesis and vascular hyperpermeability
    Issbrücker, K
    Marti, HH
    Hippenstiel, S
    Springmann, G
    Voswinckel, R
    Gaumann, A
    Breier, G
    Drexler, HCA
    Suttorp, N
    Clauss, M
    [J]. FASEB JOURNAL, 2002, 16 (14) : 262 - +
  • [15] CULTURE OF HUMAN ENDOTHELIAL CELLS DERIVED FROM UMBILICAL VEINS - IDENTIFICATION BY MORPHOLOGIC AND IMMUNOLOGICAL CRITERIA
    JAFFE, EA
    NACHMAN, RL
    BECKER, CG
    MINICK, CR
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1973, 52 (11) : 2745 - 2756
  • [16] Treatment of corneal neovascularization with dietary isoflavonoids and flavonoids
    Joussen, AM
    Rohrschneider, K
    Reichling, J
    Kirchhof, B
    Kruse, FE
    [J]. EXPERIMENTAL EYE RESEARCH, 2000, 71 (05) : 483 - 487
  • [17] Cancer phytotherapeutics: Role for flavonoids at the cellular level
    Kale, Anup
    Gawande, Sonia
    Kotwal, Swati
    [J]. PHYTOTHERAPY RESEARCH, 2008, 22 (05) : 567 - 577
  • [18] Kanadaswami C, 2005, IN VIVO, V19, P895
  • [19] KANDASWAMI C, 1994, ADV EXP MED BIOL, V366, P351
  • [20] Sphingosine 1-phosphate induces angiogenesis: Its angiogenic action and signaling mechanism in human umbilical vein endothelial cells
    Lee, OH
    Kim, YM
    Lee, YM
    Moon, EJ
    Lee, DJ
    Kim, JH
    Kim, KW
    Kwon, YG
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 264 (03) : 743 - 750
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