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

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.

• Authors: Hyo-Jeong Lee, Seung-Ae Kim, Hyo-Jung Lee, Soo-Jin Jeong, Ihn Han, Ji Hoon Jung, Eun-Ok Lee, Shudong Zhu, Chang-Yan Chen, Sung-Hoon Kim
• Journal: PloS one (PLoS One) Vol. 5 Issue 8 Pg. e12358 (Aug 23 2010) ISSN: 1932-6203 [Electronic] United States
• PMID: 20808805 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acetophenones
• Oximes
• Vascular Endothelial Growth Factor A
• paeonol oxime
• Fibroblast Growth Factor 2
• paeonol
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Acetophenones (pharmacology, therapeutic use)
• Animals
• Capillaries (cytology, drug effects)
• Cell Differentiation (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Chickens
• Chorioallantoic Membrane (drug effects, metabolism)
• Down-Regulation (drug effects)
• Endothelial Cells (cytology, drug effects)
• Fibroblast Growth Factor 2 (antagonists & inhibitors, pharmacology)
• Fibrosarcoma (blood supply, metabolism, pathology)
• Humans
• Neovascularization, Pathologic (chemically induced, drug therapy)
• Oximes (pharmacology, therapeutic use)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)
• Umbilical Veins (cytology)
• Vascular Endothelial Growth Factor A (metabolism)