A novel compound, NP-184, inhibits the vascular endothelial growth factor induced angiogenesis
Journal
European Journal of Pharmacology
Journal Volume
630
Journal Issue
1月3日
Pages
53-60
Date Issued
2010
Author(s)
Abstract
Angiogenesis is observed in many diseases, such as tumor progression, diabetes and rheumatoid arthritis; it is a process that involves proliferation, migration, differentiation and tube formation of endothelial cells. Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis by induction of these endothelial functions. Thus, inhibition of these critical angiogenic steps is a practical therapeutic strategy for those diseases. NP-184 is a substituted benzimidazole analogue which exhibits a potent anti-thrombotic activity. In this report, NP-184 inhibited the viability of human umbilical vascular endothelial cells (HUVEC) in a concentration-dependent manner, and caused cell apoptosis as examined by cell-cycle analysis and Annexin V staining with flow cytometry. NP-184 also concentration-dependently inhibited the HUVEC migration, tube formation on Matrigel, and rat aortic ring sprouting stimulated by VEGF. Regarding the intracellular signal transduction, NP-184 concentration-dependently interfered with the activation of AKT, ERK and the nuclear translocation of NF-ΚB. In vivo study showed that NP-184 dose-dependently reduced angiogenesis in Matrigel plug assay. These results indicate that NP-184 is a potential candidate for developing the treatment of angiogenesis related-diseases. ? 2009 Elsevier B.V.
SDGs
Other Subjects
2 (5 methyl 2 furyl)benzimidazole; benzimidazole derivative; immunoglobulin enhancer binding protein; lipocortin 5; matrigel; mitogen activated protein kinase 1; mitogen activated protein kinase 3; np 184; protein kinase B; unclassified drug; vasculotropin; angiogenesis; animal experiment; antiangiogenic activity; apoptosis; article; cell cycle progression; cell differentiation; cell migration; cell proliferation; cell viability; concentration (parameters); controlled study; drug dose comparison; drug structure; endothelium cell; enzyme activation; flow cytometry; gel mobility shift assay; human; human cell; in vivo study; inhibition kinetics; mouse; nonhuman; priority journal; signal transduction; thrombocyte aggregation inhibition; umbilical vein; vascular endothelium; vascular ring; Angiogenesis Inhibitors; Benzimidazoles; Cell Survival; Cells, Cultured; Dose-Response Relationship, Drug; Endothelial Cells; Endothelium, Vascular; Humans; Neovascularization, Pathologic; Umbilical Veins; Vascular Endothelial Growth Factor A
Type
journal article