Biological and Pharmaceutical Bulletin
Online ISSN : 1347-5215
Print ISSN : 0918-6158
ISSN-L : 0918-6158
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Paeonol Exerts Anti-angiogenic and Anti-metastatic Activities through Downmodulation of Akt Activation and Inactivation of Matrix Metalloproteinases
Seung-Ae Kim, Hyo-Jeong Lee, Kwang Seok Ahn, Hyo-Jung Lee, Eun-Ok Lee, Kyoo-Seok Ahn, Seung-Hoon Choi, Soo-Jin Jung, Ji Young Kim, Namin Baek, Sung-Hoon Kim
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Keywords: paeonol, basic fibroblast growth factor, human umbilical vein endothelial cell, angiogenesis, Akt
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2009 Volume 32 Issue 7 Pages 1142-1147

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Abstract

Paeonol (2′-hydroxy-4′-methoxyacetophenone) is known to possess anti-inflammatory and anti-proliferative activities. Recently there is evidence that anti-inflammatory agents may be useful in the setting of angiogenesis-related diseases. Thus in the present study the anti-angiogenic activity of paeonol and its mechanism were investigated in vitro and in vivo. Paeonol significantly inhibited proliferation of basic fibroblast growth factor (bFGF)-stimulated human umbilical vein endothelial cells (HUVECs). Paeonol also significantly inhibited migration and tube formation of bFGF-stimulated HUVECs in vitro. In addition, paeonol significantly suppressed neovessel formation on bFGF-treated chick chorioallantoic membrane (CAM) and disrupted bFGF-induced neovascularization in Matrigel plug assay in vivo. Furthermore, paeonol downregluated Akt phosphorylation in bFGF-stimulated HUVECs and reduced expression of matrix metalloproteinases-2 and -9 in HT1080 human fibrosarcoma cells. The Akt inhibitor LY294002 synergistically potentiated paeonol-induced inactivation of Akt and vascular endothelial growth factor in bFGF-treated HUVECs. Taken together, these findings suggest that paeonol can be a potent suppressor of angiogenesis and metastasis partially through inhibition of Akt signaling pathway and matrix metalloproteinase activity.

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© 2009 The Pharmaceutical Society of Japan
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