LYG-202, a newly synthesized flavonoid, exhibits potent anti-angiogenic activity in vitro and in vivo.
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.
Chen
Yan
Y
Jiangsu Key Laboratory of Carcinogenesis and Intervention (China Pharmaceutical University), People's Republic of China.
Lu
Na
N
Ling
Yun
Y
Wang
Ling
L
You
Qidong
Q
Li
Zhiyu
Z
Guo
Qinglong
Q
D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002645:Chickens; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D047309:Flavones / Q000138:chemical synthesis / Q000494:pharmacology*; D005419:Flavonoids / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D008870:Microtubules / Q000187:drug effects / Q000502:physiology; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000502:physiology
D020533:Angiogenesis Inhibitors; D047309:Flavones; D005419:Flavonoids; C541987:LYG 202; D010879:Piperazines; D042461:Vascular Endothelial Growth Factor A