A novel compound, NP-184, inhibits the vascular endothelial growth factor induced angiogenesis.
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-kappaB. 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.
Lin
Kuan-Ting
KT
Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Lien
Jin-Cherng
JC
Chung
Ching-Hu
CH
Kuo
Sheng-Chu
SC
Huang
Tur-Fu
TF
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
C549544:2-(5-methyl-2-furyl)benzimidazole; D020533:Angiogenesis Inhibitors; D001562:Benzimidazoles; D042461:Vascular Endothelial Growth Factor A