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


RESULTS
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
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.
Lee
Hyo-Jeong
HJ
College of Oriental Medicine, Kyung Hee University, Seoul, Republic of Korea.
Kim
Seung-Ae
SA
Lee
Hyo-Jung
HJ
Jeong
Soo-Jin
SJ
Han
Ihn
I
Jung
Ji Hoon
JH
Lee
Eun-Ok
EO
Zhu
Shudong
S
Chen
Chang-Yan
CY
Kim
Sung-Hoon
SH
D000098:Acetophenones / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002196:Capillaries / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005354:Fibrosarcoma / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000188:drug therapy*; D010091:Oximes / Q000494:pharmacology* / Q000627:therapeutic use; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D000098:Acetophenones; D010091:Oximes; D042461:Vascular Endothelial Growth Factor A; C553237:paeonol oxime; D016222:Fibroblast Growth Factor 2; C013638:paeonol; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
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