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.
College of Pharmacy, Seoul National University, Seoul, Korea.
Gi Dae
GD
Kim
Song Yi
SY
Bae
Hyun-Joo
HJ
Park
Kihwan
K
Bae
Sang Kook
SK
Lee
D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D058732:Embryoid Bodies / Q000187:drug effects / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D017705:Lignans / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D000498:Allyl Compounds; D010636:Phenols
D020533:Angiogenesis Inhibitors; D001713:Biphenyl Compounds; D017705:Lignans; D020929:Mitogen-Activated Protein Kinase Kinases; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D058570:TOR Serine-Threonine Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols