Myoseverin is a potential angiogenesis inhibitor by inhibiting endothelial cell function and endothelial progenitor cell differentiation.
Myoseverin, a new microtubule-binding molecule, acts reversibly on myoblast proliferation without the cytotoxic effects displayed by nonpurine-based microtubule-disrupting molecules, like taxol, vinblastine, nocodazole, and the colchicines. In this study, we examined the effects of myoseverin on in vitro function of endothelial cells and endothelial progenitor cell differentiation in order to explore the possibility for the application of myoseverin as a reversible antiangiogenic agent. Myoseverin potently inhibited proliferation of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner with an IC50 of approximately 8 microM. When myoseverin was removed after treatment for 3 days, all the cells pretreated at a concentration range of 2.5-80 microM resumed the cell growth. It also inhibited VEGF-induced HUVEC migration dose dependently. When mononuclear cells (MNCs) isolated from human cord blood were cultured on fibronectin-coated plates for 7 days, myoseverin decreased the number of adherent cells in a dose-dependent manner with IC50 of approximately 9 microM. It also suppressed the development of ac-LDL uptake ability as well as the expression of endothelial lineage markers, KDR, CD31, and vWF. Finally, it inhibited formation of HUVECs or ex vivo cultivated EPCs into capillary-like structure on Matri-gel and in vivo angiogenesis on the chick chorioallantoic membrane. Therefore, these results suggest that myoseverin can be effectively used for the inhibition of new vessel growth by inhibiting endothelial cell function and differentiation of progenitor cells.
Park
Hyo-Eun
HE
Department of Biomedical Sciences, Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Baek
Sang Hong
SH
Min
Jaeki
J
Chang
Young-Tae
YT
Kang
Dong-Ku
DK
Chang
Soo-Ik
SI
Joe
Young Ae
YA
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008077:Lipoproteins, LDL / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011687:Purines / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D008077:Lipoproteins, LDL; D011687:Purines; C032629:acetyl-LDL; C407365:myoseverin