Honokiol Inhibits Vascular Vessel Formation of Mouse Embryonic Stem Cell-Derived Endothelial Cells via the Suppression of PECAM and MAPK/mTOR Signaling Pathway

Cellular Physiology and Biochemistry

关键词: Honokiol;    Anti-angiogenesis;    PECAM;    Differentiation;    MAPK;    mTOR;    Mouse embryonic stem cells;   

DOI  :  10.1159/000341455

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

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.

【 授权许可】

CC BY-NC-ND