Abstract
Although antofine, a natural phenanthroindolizidine alkaloid, exerts potential biological activities, including anticancer effect and anti-angiogenic activity, the underlying mechanisms have not yet been investigated. In the present study, the inhibitory effect of antofine on angiogenesis was determined in cultured mouse embryonic stem (mES)/embryoid body (EB)-derived endothelial cells and vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cells (HUVECs). Antofine effectively inhibited VEGF-induced cell migration and tube formation of HUVECs. Antofine also significantly decreased ex vivo microvessel sprouting in cultured mouse aortic rings, and inhibited the vascular formation and platelet/endothelial cell adhesion molecule (PECAM) expression of mES/EB-derived cells in 3-D collagen gel. The underlying mechanism of anti-angiogenic activity of antofine was, in part, associated with the modulation of AKT/mTOR and AMP-activated protein kinase (AMPK) signaling in VEGF-stimulated HUVECs.
Keywords:
AKT/mTOR; AMPK; Angiogenesis; Antofine; HUVECs.
Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
MeSH terms
-
AMP-Activated Protein Kinases / genetics
-
AMP-Activated Protein Kinases / metabolism*
-
Angiogenesis Inhibitors / pharmacology*
-
Animals
-
Cell Proliferation / drug effects
-
Endothelial Progenitor Cells / cytology
-
Endothelial Progenitor Cells / drug effects*
-
Endothelial Progenitor Cells / metabolism
-
Humans
-
Indoles / pharmacology*
-
Indolizines / pharmacology
-
Mice
-
Mouse Embryonic Stem Cells / cytology
-
Mouse Embryonic Stem Cells / drug effects*
-
Mouse Embryonic Stem Cells / metabolism
-
Neovascularization, Pathologic / drug therapy
-
Neovascularization, Pathologic / genetics
-
Neovascularization, Pathologic / metabolism*
-
Neovascularization, Pathologic / physiopathology
-
Phenanthrolines / pharmacology*
-
Proto-Oncogene Proteins c-akt / genetics
-
Proto-Oncogene Proteins c-akt / metabolism*
-
Signal Transduction / drug effects
-
TOR Serine-Threonine Kinases / genetics
-
TOR Serine-Threonine Kinases / metabolism*
-
Vascular Endothelial Growth Factor A / genetics
-
Vascular Endothelial Growth Factor A / metabolism
Substances
-
Angiogenesis Inhibitors
-
Indoles
-
Indolizines
-
Phenanthrolines
-
Vascular Endothelial Growth Factor A
-
antofine
-
phenanthroindolizidine
-
Proto-Oncogene Proteins c-akt
-
TOR Serine-Threonine Kinases
-
AMP-Activated Protein Kinases