Anti-angiogenic activity of torilin, a sesquiterpene compound isolated from Torilis japonica.
Torilin is a sesquiterpene compound purified from fruits of Torilis japonica (Umbelliferae). In this study, we demonstrated the anti-angiogenic activity of torilin using in vivo and in vitro assay systems. Torilin decreased both neovascularization of chick embryos in the chorioallantoic membrane assay and basic fibroblast growth factor-induced vessel formation in the mouse Matrigel plug assay. Torilin also reduced the proliferation and tube formation of human umbilical vein endothelial cells. In addition, the concentrated conditioned media obtained from torilin-treated HepG2 human hepatoblastoma cells blocked the angiogenic activation of torilin-untreated concentrated conditioned media, indicating that torilin may have an inhibitory effect on tumor-induced angiogenesis. To determine what molecules were involved in the anti-angiogenic activity, we examined the expression of hypoxia-inducible angiogenic factors in torilin-treated HepG2 cells. Torilin significantly down-regulated the expression of hypoxia-inducible vascular endothelial growth factor and insulin-like growth factor-II. Taken together, our data suggest that torilin may be a strong angiogenic inhibitor with the ability to decrease tube formation of vascular endothelial cells and to reduce expression of angiogenic factors of tumor cells.
Kim
M S
MS
Department of Molecular Biology, Pusan National University, Pusan, South Korea.
Lee
Y M
YM
Moon
E J
EJ
Kim
S E
SE
Lee
J J
JJ
Kim
K W
KW
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D015536:Down-Regulation; D004338:Drug Combinations; D016228:Endothelial Growth Factors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic; D010936:Plant Extracts / Q000494:pharmacology*; D011509:Proteoglycans / Q000378:metabolism; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D045789:Sesquiterpenes, Guaiane; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D017077:Culture Media, Conditioned; D004338:Drug Combinations; D016228:Endothelial Growth Factors; D007797:Laminin; D008222:Lymphokines; D010936:Plant Extracts; D011509:Proteoglycans; D012717:Sesquiterpenes; D045789:Sesquiterpenes, Guaiane; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; C059485:matrigel; D007335:Insulin-Like Growth Factor II; D003094:Collagen; C112694:torilin