LYG-202, a newly synthesized flavonoid, exhibits potent anti-angiogenic activity in vitro and in vivo

Journal of Pharmacological Sciences

Volumn 112, Issue 1, 2010, Pages 37-45

  Chen, Yan ^a   Lu, Na ^a   Ling, Yun ^a   Wang, Ling ^a   You, Qidong ^a   Li, Zhiyu ^a   Guo, Qinglong ^a  

^a CHINA PHARMACEUTICAL UNIVERSITY   (China)

Author keywords

Angiogenesis; Flavonoid; Human umbilical vein endothelial cell (HUVEC); KDR Flk 1 (VEGFR 2); Vascular endothelial growth factor (VEGF)

Indexed keywords

FLAVONOID; LYG 202; PROTEIN KINASE B; UNCLASSIFIED DRUG; VASCULOTROPIN;

ANGIOGENESIS; ANTIANGIOGENIC ACTIVITY; ARTICLE; CELL MIGRATION; FETUS MEMBRANE; HUMAN; IN VITRO STUDY; IN VIVO STUDY; NONHUMAN; RAT;

EID: 75749150162     PISSN: 13478613     EISSN: 13478648     Source Type: Journal    
DOI: 10.1254/jphs.09213FP     Document Type: Article

References (38)

1. Havsteen BH. The biochemistry and medical significance of the flavonoids. Pharmacol Ther. 2002;96:67-202.
2. Ren W, Qiao Z, Wang H, Zhu L, Zhang L. Flavonoids: promising anticancer agents. Med Res Rev. 2003;23:519-534.
3. Kandaswami C, Middleton E, Jr. Free radical scavenging and antioxidant activity of plant flavonoids. Adv Exp Med Biol. 1994;366:351-376.
4. Mojzis J, Varinska L, Mojzisova G, Kostova I, Mirossay L. Antiangiogenic effects of flavonoids and chalcones. Pharmacol Res. 2008;57:259-265.
5. Risau W. Mechanisms of angiogenesis. Nature. 1997;386: 671-674.
6. Carmeliet P. Angiogenesis in life, disease and medicine. Nature. 2005;438:932-936.
7. Nyberg P, Xie L, Kalluri R. Endogenous inhibitors of angiogenesis. Cancer Res. 2005;65:3967-3979.
8. Oak MH, El Bedoui J, Schini-Kerth VB. Antiangiogenic properties of natural polyphenols from red wine and green tea. J Nutr Biochem. 2005;16:1-8.
9. Joussen AM, Rohrschneider K, Reichling J, Kirchhof B, Kruse FE. Treatment of corneal neovascularization with dietary isoflavonoids and flavonoids. Exp Eye Res. 2000;71:483-487.
10. Dulak J. Nutraceuticals as anti-angiogenic agents: hopes and reality. J Physiol Pharmacol. 2005;56 Suppl 1:51-67.
11. Kandaswami C, Lee LT, Lee PP, Hwang JJ, Ke FC, Huang YT, et al. The antitumor activities of flavonoids. In Vivo. 2005;19:895-909.
12. Kale A, Gawande S, Kotwal S. Cancer phytotherapeutics: role for flavonoids at the cellular level. Phytother Res. 2008;22:567-577.
13. Jaffe EA, Nachman RL, Becker CG, Minick CR. Culture of human endothelial cells derived from umbilical veins. Identification by morphologic and immunologic criteria. J Clin Invest. 1973;52:2745-2756.
14. Lee OH, Kim YM, Lee YM, Moon EJ, Lee DJ, Kim JH, et al. Sphingosine 1-phosphate induces angiogenesis: its angiogenic action and signaling mechanism in human umbilical vein endothelial cells. Biochem Biophys Res Commun. 1999;264:743-750.
15. Ashton AW, Yokota R, John G, Zhao S, Suadicani SO, Spray DC, et al. Inhibition of endothelial cell migration, intercellular communication, and vascular tube formation by thromboxane A(2). J Biol Chem. 1999;274:35562-35570.
16. Ling Y, Yang Y, Lu N, You QD, Wang S, Gao Y, et al. Endostar, a novel recombinant human endostatin, exerts antiangiogenic effect via blocking VEGF-induced tyrosine phosphorylation of KDR/Flk-1 of endothelial cells. Biochem Biophys Res Commun. 2007;361:79-84.
17. Lu N, Yang Y, You QD, Ling Y, Gao Y, Gu HY, et al. Gambogic acid inhibits angiogenesis through suppressing vascular endothelial growth factor-induced tyrosine phosphorylation of KDR/Flk-1. Cancer Lett. 2007;258:80-89.
18. Lu N, Gao Y, Ling Y, Chen Y, Yang Y, Gu HY, et al. Wogonin suppresses tumor growth in vivo and VEGF-induced angiogenesis through inhibiting tyrosine phosphorylation of VEGFR2. Life Sci. 2008;82:956-963.
19. Carmeliet P, Ferreira V, Breier G, Pollefeyt S, Kieckens L, Gertsenstein M, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 1996;380:435-439.
20. Pepper MS, Wasi S, Ferrara N, Orci L, Montesano R. In vitro angiogenic and proteolytic properties of bovine lymphatic endothelial cells. Exp Cell Res. 1994;210:298-305.
21. Hanahan D, Christofori G, Naik P, Arbeit J. Transgenic mouse models of tumour angiogenesis: the angiogenic switch, its molecular controls, and prospects for preclinical therapeutic models. Eur J Cancer. 1996;32A:2386-2393.
22. Patan S. Vasculogenesis and angiogenesis as mechanisms of vascular network formation, growth and remodeling. J Neurooncol. 2000;50:1-15.
23. Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev. 1997;18:4-25.
24. Cross MJ, Claesson-Welsh L. FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol Sci. 2001;22:201-207.
25. Autiero M, Luttun A, Tjwa M, Carmeliet P. Placental growth factor and its receptor, vascular endothelial growth factor receptor-1: novel targets for stimulation of ischemic tissue revascularization and inhibition of angiogenic and inflammatory disorders. J Thromb Haemost. 2003;1:1356-1370.
26. Veikkola T, Karkkainen M, Claesson-Welsh L, Alitalo K. Regulation of angiogenesis via vascular endothelial growth factor receptors. Cancer Res. 2000;60:203-212.
27. Neufeld G, Cohen T, Gengrinovitch S, Poltorak Z. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J. 1999;13:9-22.
28. Zachary I, Gliki G. Signaling transduction mechanisms mediating biological actions of the vascular endothelial growth factor family. Cardiovasc Res. 2001;49:568-581.
29. Rousseau S, Houle F, Kotanides H, Witte L, Waltenberger J, Landry J, et al. Vascular endothelial growth factor (VEGF)-driven actin-based motility is mediated by VEGFR2 and requires concerted activation of stress-activated protein kinase 2 (SAPK2/p38) and geldanamycin-sensitive phosphorylation of focal adhesion kinase. J Biol Chem. 2000;275:10661-10672.
30. Gerber HP, McMurtrey A, Kowalski J, Yan M, Keyt BA, Dixit V, et al. Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3′-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation. J Biol Chem. 1998;273:30336-30343.
31. Somanath PR, Malinin NL, Byzova TV. Cooperation between integrin alpha(nu)beta (3) and VEGFR2 in angiogenesis. Angiogenesis. 2009;12:177-185.
32. Ogawa S, Oku A, Sawano A, Yamaguchi S, Yazaki Y, Shibuya M. A novel type of vascular endothelial growth factor, VEGF-E (NZ-7 VEGF), preferentially utilizes KDR/Flk-1 receptor and carries a potent mitotic activity without heparin-binding domain. J Biol Chem. 1998;273:31273-31282.
33. Cunningham BD, Threadgill MD, Groundwater PW, Dale IL, Hickman JA. Synthesis and biological evaluation of a series of flavones designed as inhibitors of protein tyrosine kinases. Anticancer Drug Des. 1992;7:365-384.
34. Six I, Kureishi Y, Luo Z, Walsh K. Akt signaling mediates VEGF/VPF vascular permeability in vivo. FEBS Lett. 2002;532:67-69.
35. Huang D, Ding Y, Luo WM, Bender S, Qian CN, Kort E, et al. Inhibition of MAPK kinase signaling pathways suppressed renal cell carcinoma growth and angiogenesis in vivo. Cancer Res. 2008;68:81-88.
36. Issbrucker K, Marti HH, Hippenstiel S, Springmann G, Voswinckel R, Gaumann A, et al. p38 MAP kinase - a molecular switch between VEGF-induced angiogenesis and vascular hyper-permeability. FASEB J. 2003;17:262-264.
37. Zeng S, Liu W, Nie FF, Zhao Q, Rong JJ, Wang J, et al. LYG-202, a new flavonoid with a piperazine substitution, shows antitumor effects in vivo and in vitro. Biochem Biophys Res Commun. 2009;385:551-556.
38. Folkman J, Shing Y. Angiogenesis. J Biol Chem. 1992;267: 10931-10934.