Wogonin suppresses tumor growth in vivo and VEGF-induced angiogenesis through inhibiting tyrosine phosphorylation of VEGFR2.
Previous studies revealed that wogonin, a naturally occurring monoflavonoid extracted from Scutellariae radix, possessed anticancer activity both in vitro and in vivo. However, the molecular mechanism of its potent anticancer activity remains poorly understood and warrants further investigations. In this study, we found for the first time that wogonin inhibited the growth and tumor angiogenesis of human gastric carcinoma in nude mice. We explored the inhibitory effect of wogonin on angiogenesis stimulated by vascular endothelial growth factor (VEGF) in vitro. Wogonin suppressed the VEGF-stimulated migration and tube formation of human umbilical vein endothelial cells (HUVECs). It also restrained VEGF-induced tyrosine phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2). This inhibition of receptor phosphorylation was correlated with a significant decrease in VEGF-triggered phosphorylated forms of ERK, AKT and p38. Taken together, these findings strongly suggest that wogonin might be a promising antitumor drug.
Lu
Na
N
Jiangsu Key Laboratory of Carcinogenesis and Intervention (China Pharmaceutical University), Nanjing 210009, People's Republic of China.
Gao
Ying
Y
Ling
Yun
Y
Chen
Yan
Y
Yang
Yong
Y
Gu
Hong-Yan
HY
Qi
Qi
Q
Liu
Wei
W
Wang
Xiao-Tang
XT
You
Qi-Dong
QD
Guo
Qing-Long
QL
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D044950:Flavanones / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D008870:Microtubules / Q000187:drug effects; D009368:Neoplasm Transplantation; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000187:drug effects / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D044950:Flavanones; D016166:Free Radical Scavengers; D042461:Vascular Endothelial Growth Factor A; D014443:Tyrosine; D040301:Vascular Endothelial Growth Factor Receptor-2; D048051:p38 Mitogen-Activated Protein Kinases; C085514:wogonin