期刊
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
卷 30, 期 3, 页码 758-770出版社
KARGER
DOI: 10.1159/000341455
关键词
Honokiol; Anti-angiogenesis; PECAM; Differentiation; MAPK; mTOR; Mouse embryonic stem cells
资金
- National Research Foundation of Korea (NRF)
- Korean Government (MEST) (MRC) [2011-30635]
- Korean Government (MEST) [NRF-2010-355-E00069]
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 anti-angiogenic 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 gelatin-coated 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. Copyright (C) 2012 S. Karger AG, Basel
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