KR-31831, a new synthetic anti-ischemic agent, inhibits in vivo and in vitro angiogenesis.
Angiogenesis is considered to be an integral process to the growth and spread of solid tumors. Anti-angiogenesis therapy recently has been found to be one of the most promising anti-cancer therapeutic strategies. In this study, we provide several lines of evidences showing that KR-31831, a new benzopyran derivative, has anti-angiogenic activities. KR-31831 inhibited the proliferation, migration, invasion and tube formation of bovine aortic endothelial cells (BAECs), and suppressed the release of matrix metalloproteinase-2 (MMP-2) of BAECs. KR-31831 also inhibited in vivo angiogenesis in mouse Matrigel plug assay. Furthermore, the mRNA expressions of basic fibroblast growth factor (bFGF), fibroblast growth factor receptor-2 (FGFR-2), and vascular endothelial growth factor receptor-2 (VEGFR-2) were decreased by KR-31831. Taken together, these results suggest that KR-31831 acts as a novel angiogenesis inhibitor and might be useful for treating hypervascularized cancers.
Yi
Eui-Yeun
EY
Department of Molecular Biology, Pusan National University, Busan 609-735, Korea.
Park
Shi-Young
SY
Song
Hyun Seok
HS
Son
Myung Jin
MJ
Yi
Kyu-Yang
KY
Yoo
Sung-En
SE
Kim
Yung-Jin
YJ
D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology* / Q000627:therapeutic use; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D007511:Ischemia / Q000188:drug therapy; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D001578:Benzopyrans; D007093:Imidazoles; C503693:KR 31831; D016222:Fibroblast Growth Factor 2; D051497:Receptor, Fibroblast Growth Factor, Type 2; D040301:Vascular Endothelial Growth Factor Receptor-2; D020778:Matrix Metalloproteinase 2