Decursin and decursinol inhibit VEGF-induced angiogenesis by blocking the activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase.
The root of Angelica gigas Nakai contains two major coumarins, which have been previously identified as decursin and decursinol. Decursin has been demonstrated to exhibit potent anti-cancer activity both in vitro and in vivo. In this study, we found that decursin and decursinol at non-cytotoxic doses inhibited the VEGF-induced proliferation, migration, and capillary-tube formation of HUVECs. Moreover, decursin and decursinol suppressed microvessel formation on chorioallantoic membranes in fertilized eggs and into mouse Matrigel plugs. The oral administration of decursin and decursinol also reduced VEGF-induced angiogenesis in Matrigel. Furthermore, decursin and decursinol reduced the phosphorylation of ERK and JNK, but not p38 MAPK, in VEGF-stimulated HUVECs. Taken together, our results reveal that decursin and decursinol inhibit VEGF-induced angiogenesis by reducing the activation of ERK and JNK in HUVECs, and possess potent in vivo anti-angiogenic activity, coupled with the advantage of oral dosing. Thus, these compounds may have the potential for the treatment of cancers dependent on VEGF-induced vascularization.
Son
Seung Hwa
SH
Department of Oral Biology, Oral Cancer Research Institute, Oral Science Research Institute, and Brain Korea 21 Project, Yonsei University College of Dentistry, Seoul 120-752, Republic of Korea.
Kim
Mi-Jeong
MJ
Chung
Won-Yoon
WY
Son
Ju-Ah
JA
Kim
Yeong Shik
YS
Kim
Young-Choong
YC
Kang
Sam Sik
SS
Lee
Sang-Kook
SK
Park
Kwang-Kyun
KK
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002087:Butyrates / Q000494:pharmacology*; D002465:Cell Movement; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic; D010936:Plant Extracts / Q000378:metabolism; D018517:Plant Roots / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D001578:Benzopyrans; D002087:Butyrates; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; C101278:decursin; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases