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Paeonol oxime inhibits bFGF-induced angiogenesis and reduces VEGF levels in fibrosarcoma cells.

Lee HJ, Kim SA, Lee HJ, Jeong SJ, Han I, Jung JH, Lee EO, Zhu S, Chen CY, Kim SH - PLoS ONE (2010)

Bottom Line: The treatment with PO at 12.5 microg/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.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.

View Article: PubMed Central - PubMed

Affiliation: College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea.

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 (IC(50) = 17.3 microg/ml) significantly inhibited bFGF-induced cell proliferation, which was achieved with higher concentrations of paeonol (IC(50) over 200 microg). 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 microg/ml) decreased the cell viability of HT-1080 fibrosarcoma cells but not that of HUVECs. The treatment with PO at 12.5 microg/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.

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Related in: MedlinePlus

Chemical structure of paeonol oxime.Paeonol oxime (PO) (1-[2-hydroxy-4-methoxy phenyl] ethanone oxime) was synthesized from paeonol.
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pone-0012358-g001: Chemical structure of paeonol oxime.Paeonol oxime (PO) (1-[2-hydroxy-4-methoxy phenyl] ethanone oxime) was synthesized from paeonol.

Mentions: Paeonol oxime (1-[2-hydroxy-4-methoxy phenyl] ethanone oxime; PO) was derived from paeonol (2-hydroxy, 4-methoxy acetophenone), which has been shown to be anti-angiogenic [13] (Fig. 1). We designed and synthesized PO so that it also shares some similarity with acetylsalicylic acid (Fig. 1), a well known anti-inflammatory pain killer but also with anti-angiogenic activity [1], [14], with the goal to achieve better solubility and anti-angiogenic potency than paeonol. In this regard, we tested the anti-angiogenic properties of PO on bFGF-stimulated human umbilical vein endothelial cells (HUVECs) by examining proliferation, migration, tube formation and chick chorioallantoic membrane (CAM). We also explored the potential signaling events affected by PO in angiogenic HT-1080 cells by Western blotting and immunofluorescence microscopy.


Paeonol oxime inhibits bFGF-induced angiogenesis and reduces VEGF levels in fibrosarcoma cells.

Lee HJ, Kim SA, Lee HJ, Jeong SJ, Han I, Jung JH, Lee EO, Zhu S, Chen CY, Kim SH - PLoS ONE (2010)

Chemical structure of paeonol oxime.Paeonol oxime (PO) (1-[2-hydroxy-4-methoxy phenyl] ethanone oxime) was synthesized from paeonol.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2925949&req=5

pone-0012358-g001: Chemical structure of paeonol oxime.Paeonol oxime (PO) (1-[2-hydroxy-4-methoxy phenyl] ethanone oxime) was synthesized from paeonol.
Mentions: Paeonol oxime (1-[2-hydroxy-4-methoxy phenyl] ethanone oxime; PO) was derived from paeonol (2-hydroxy, 4-methoxy acetophenone), which has been shown to be anti-angiogenic [13] (Fig. 1). We designed and synthesized PO so that it also shares some similarity with acetylsalicylic acid (Fig. 1), a well known anti-inflammatory pain killer but also with anti-angiogenic activity [1], [14], with the goal to achieve better solubility and anti-angiogenic potency than paeonol. In this regard, we tested the anti-angiogenic properties of PO on bFGF-stimulated human umbilical vein endothelial cells (HUVECs) by examining proliferation, migration, tube formation and chick chorioallantoic membrane (CAM). We also explored the potential signaling events affected by PO in angiogenic HT-1080 cells by Western blotting and immunofluorescence microscopy.

Bottom Line: The treatment with PO at 12.5 microg/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.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.

View Article: PubMed Central - PubMed

Affiliation: College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea.

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 (IC(50) = 17.3 microg/ml) significantly inhibited bFGF-induced cell proliferation, which was achieved with higher concentrations of paeonol (IC(50) over 200 microg). 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 microg/ml) decreased the cell viability of HT-1080 fibrosarcoma cells but not that of HUVECs. The treatment with PO at 12.5 microg/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.

Show MeSH
Related in: MedlinePlus