Paeonol Oxime Inhibits bFGF-Induced Angiogenesis and Reduces VEGF Levels in Fibrosarcoma Cells

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Paeonol Oxime Inhibits bFGF-Induced Angiogenesis and Reduces VEGF Levels in Fibrosarcoma Cells

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Title: Paeonol Oxime Inhibits bFGF-Induced Angiogenesis and Reduces VEGF Levels in Fibrosarcoma Cells
Author: Lee, Hyo-Jeong; Kim, Seung-Ae; Lee, Hyo-Jung; Jeong, Soo-Jin; Han, Ihn; Lee, Eun-Ok; Kim, Sung-Hoon; Jung, Ji Hoon; Zhu, Shudong; Chen, Chang-Yan

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Citation: Lee, Hyo-Jeong, Seung-Ae Kim, Hyo-Jung Lee, Soo-Jin Jeong, Ihn Han, Ji Hoon Jung, Eun-Ok Lee, Shudong Zhu, Chang-Yan Chen, and Sung-Hoon Kim. 2010. Paeonol oxime inhibits bFGF-induced angiogenesis and reduces VEGF levels in fibrosarcoma cells. PLoS ONE 5(8): e12358.
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Abstract: Background: We previously reported the anti-angiogenic activity of paeonol isolated from Moutan Cortex. In the present study, we investigated the negative effect of paeonol oxime (PO, a paeonol derivative) on basic fibroblast growth factor (bFGF)-mediated angiogenesis in human umbilical vein endothelial cells (HUVECs) (including tumor angiogenesis) and pro-survival activity in HT-1080 fibrosarcoma cell line. Methodology/Principal Findings: We showed that PO (IC50  = 17.3 µg/ml) significantly inhibited bFGF-induced cell proliferation, which was achieved with higher concentrations of paeonol (IC50 over 200 µg). The treatment with PO blocked bFGF-stimulated migration and in vitro capillary differentiation (tube formation) in a dose-dependent manner. Furthermore, PO was able to disrupt neovascularization in vivo. Interestingly, PO (25 µg/ml) decreased the cell viability of HT-1080 fibrosarcoma cells but not that of HUVECs. The treatment with PO at 12.5 µg/ml reduced the levels of phosphorylated AKT and VEGF expression (intracellular and extracelluar) in HT-1080 cells. Consistently, immunefluorescence imaging analysis revealed that PO treatment attenuated AKT phosphorylation in HT-1080 cells. Conclusions/Significance: Taken together, these results suggest that PO inhibits bFGF-induced angiogenesis in HUVECs and decreased the levels of PI3K, phospho-AKT and VEGF in HT-1080 cells.
Published Version: doi:10.1371/journal.pone.0012358
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925949/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4878071

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