Honokiol inhibits vascular vessel formation of mouse embryonic stem cell-derived endothelial cells via the suppression of PECAM and MAPK/mTOR signaling pathway.

Embryonic stem cells, which are characterized by pluripotency and self-renewal, have recently been highlighted in drug discovery. In particular, the potential of ES cells to differentiate into specific-cell types make them an extremely useful tool in the evaluation of the biological activity of test compounds. Honokiol, a major neolignan derived from the bark of Magnolia obovata, has been shown an anti-tumor activity. However, the precise mechanism of action in the anti-tumor activity of honokiol is still poorly understood. Here, we evaluated the antiangiogenic activity of honokiol using mouse ES cell-derived embryoid bodies. mES-derived EBs were formed using hanging drop cultures and vascular formation was induced on gelatincoated plates in EGM-2 medium. The growth inhibition of honokiol was found to be more sensitive in the differentiated EB-derived endothelial cells compared to the undifferentiated EB-derived cells. Honokiol also inhibited the vascular formation of mES cells on 3-D collagen gel and decreased the expression of endothelial biomarkers VEGFR2 and PECAM in the differentiated EB-derived endothelial cells. In addition, honokiol suppressed the MAPK and mTOR signaling pathways in the EB-derived endothelial cells. Therefore, the anti-angiogenic activity of honokiol is associated in part with the suppression of PECAM and MAPK/mTOR pathways in EB-derived endothelial cells.

Kim GD ，Bae SY ，Park HJ ，Bae K ，Lee SK ... -  《-》

Magnolol inhibits angiogenesis by regulating ROS-mediated apoptosis and the PI3K/AKT/mTOR signaling pathway in mES/EB-derived endothelial-like cells.

Kim GD ，Oh J ，Park HJ ，Bae K ，Lee SK ... -  《-》

6"-Debromohamacanthin A, a bis (indole) alkaloid, inhibits angiogenesis by targeting the VEGFR2-mediated PI3K/AKT/mTOR signaling pathways.

Kim GD ，Cheong OJ ，Bae SY ，Shin J ，Lee SK ... -  《Marine Drugs》

Antofine, a natural phenanthroindolizidine alkaloid, suppresses angiogenesis via regulation of AKT/mTOR and AMPK pathway in endothelial cells and endothelial progenitor cells derived from mouse embryonic stem 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.

Oh J ，Kim GD ，Kim S ，Lee SK ... -  《-》

Thio-Cl-IB-MECA, a novel A₃ adenosine receptor agonist, suppresses angiogenesis by regulating PI3K/AKT/mTOR and ERK signaling in endothelial cells.

Although A₃AR agonists exhibit a variety of biological activities including anticancer effects, their possible anti-angiogenic effects have not yet been investigated. In the present study, we assayed the anti-angiogenic activity of thio-Cl-IB-MECA, a novel A₃AR agonist, in cultured HUVECs and mES/EB-derived endothelial cells. Thio-Cl-IB-MECA inhibited migration and tube formation by endothelial cells and dramatically decreased ex vivo microvessel sprouting in cultured mouse aortic rings. The anti-angiogenic activity of thio-Cl-IB-MECA was associated with suppression of the expression of the endothelial biomarker PECAM via regulation of PI3K/AKT/mTOR and ERK signaling in mES/EB-derived endothelial cells.

Kim GD ，Oh J ，Jeong LS ，Lee SK ... -  《-》