Decursin and decursinol angelate inhibit VEGF-induced angiogenesis via suppression of the VEGFR-2-signaling pathway.
Inhibition of angiogenesis is an attractive approach for the treatment of angiogenic diseases, such as cancer. Vascular endothelial growth factor (VEGF) is one of the most important activators of angiogenesis and interacts with the high-affinity tyrosine kinase receptors, VEGFR-1 and VEGFR-2. The pyranocoumarin compounds decursin and decursinol angelate isolated from the herb, Angelica gigas, are known to possess potent anti-inflammatory activities. However, little is known about their antiangiogenic activity or their underlying mechanisms. Here, we show the antiangiogenic effects of decursin and decursinol angelate using in vitro assays and in vivo animal experiments. Decursin and decursinol angelate inhibited VEGF-induced angiogenic processes in vitro, including proliferation, migration and tube formation of human umbilical vein endothelial cells. Decursin and decursinol angelate significantly suppressed neovessel formation in chick chorioallantoic membrane and tumor growth in a mouse model. The microvessel density in tumors treated with decursin for 14 days was significantly decreased compared with a vehicle control group. Decursin and decursinol angelate inhibited VEGF-induced phosphorylation of VEGFR-2, extracellular signal-regulated kinases and c-Jun N-terminal kinase mitogen-activated protein kinases. Taken together, these results demonstrate that decursin and decursinol angelate are novel candidates for inhibition of VEGF-induced angiogenesis.
Jung
Myung Hwan
MH
Department of Natural Sciences, School of Life Sciences and Biotechnology, Kyungpook National University, Daegu 702-701, Republic of Korea.
Lee
Sun Hee
SH
Ahn
Eun-Mi
EM
Lee
You Mie
YM
D000818:Animals; D030801:Animals, Genetically Modified; D019661:Apiaceae / Q000737:chemistry; D001578:Benzopyrans / Q000494:pharmacology*; D015153:Blotting, Western; D002087:Butyrates / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000098:blood supply* / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000098:blood supply; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D011493:Protein Kinase C; D015398:Signal Transduction; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish
D001578:Benzopyrans; D002087:Butyrates; D010936:Plant Extracts; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C101278:decursin; D040301:Vascular Endothelial Growth Factor Receptor-2; D011493:Protein Kinase C