Paeonol exerts anti-angiogenic and anti-metastatic activities through downmodulation of Akt activation and inactivation of matrix metalloproteinases.
Paeonol (2'-hydroxy-4'-methoxyacetophenone) is known to possess anti-inflammatory and anti-proliferative activities. Recently there is evidence that anti-inflammatory agents may be useful in the setting of angiogenesis-related diseases. Thus in the present study the anti-angiogenic activity of paeonol and its mechanism were investigated in vitro and in vivo. Paeonol significantly inhibited proliferation of basic fibroblast growth factor (bFGF)-stimulated human umbilical vein endothelial cells (HUVECs). Paeonol also significantly inhibited migration and tube formation of bFGF-stimulated HUVECs in vitro. In addition, paeonol significantly suppressed neovessel formation on bFGF-treated chick chorioallantoic membrane (CAM) and disrupted bFGF-induced neovascularization in Matrigel plug assay in vivo. Furthermore, paeonol downregluated Akt phosphorylation in bFGF-stimulated HUVECs and reduced expression of matrix metalloproteinases-2 and -9 in HT1080 human fibrosarcoma cells. The Akt inhibitor LY294002 synergistically potentiated paeonol-induced inactivation of Akt and vascular endothelial growth factor in bFGF-treated HUVECs. Taken together, these findings suggest that paeonol can be a potent suppressor of angiogenesis and metastasis partially through inhibition of Akt signaling pathway and matrix metalloproteinase activity.
Kim
Seung-Ae
SA
Cancer Preventive Material Development Research Center, College of Oriental Medicine, Kyunghee University.
Lee
Hyo-Jeong
HJ
Ahn
Kwang Seok
KS
Lee
Hyo-Jung
HJ
Lee
Eun-Ok
EO
Ahn
Kyoo-Seok
KS
Choi
Seung-Hoon
SH
Jung
Soo-Jin
SJ
Kim
Ji Young
JY
Baek
Namin
N
Kim
Sung-Hoon
SH
D000098:Acetophenones / Q000494:pharmacology* / Q000627:therapeutic use; D020533:Angiogenesis Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D054443:Cell Migration Assays; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002642:Chick Embryo; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D020778:Matrix Metalloproteinase 2; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000517:prevention & control*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*
D000098:Acetophenones; D020533:Angiogenesis Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D016222:Fibroblast Growth Factor 2; C013638:paeonol; D051057:Proto-Oncogene Proteins c-akt; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2