Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5560074 | Food and Chemical Toxicology | 2017 | 7 Pages |
â¢Antofine exhibits antitumor activity against cancer cells, but the anti-angiogenic activity has not been investigated yet.â¢Antofine exhibits the potential anti-angiogenic activity in the endothelial cells and mES-derived endothelial-like cells.â¢Antofine regulates angiogenesis via modulation of AKT/mTOR/AMPK and ERK signaling pathways in endothelial cells.
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.
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