Paeonol Oxime Inhibits bFGF-Induced Angiogenesis and Reduces VEGF Levels in Fibrosarcoma Cells
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Lee, Hyo-Jeong
Kim, Seung-Ae
Lee, Hyo-Jung
Jeong, Soo-Jin
Han, Ihn
Lee, Eun-Ok
Kim, Sung-Hoon
Jung, Ji Hoon
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https://doi.org/10.1371/journal.pone.0012358Metadata
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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.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925949/pdf/Terms of Use
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