Toona sinensis (leaf extracts) inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis in vascular endothelial cells.
OBJECTIVE
Toona sinensis is well known as a traditional Chinese medicine; also, it has been shown to exhibit anticancer and anti-inflammatory effects. This study was aimed at evaluating the anti-angiogenesis effect of the aqueous extracts of Toona sinensis (TS extracts) or gallic acid, a major component of TS extracts, against both VEGF-induced EA.hy 926 and human umbilical vein endothelial cells (HUVECs).


METHODS
Anti-proliferative activity of TS extracts or gallic acid, was determined against EA.hy 926 and HUVECs by trypan blue exclusion method. Invasion, tube formation and chick chorioallantoic membrane assay were carried out to determine the in vitro and in vivo anti-angiogenic effects.


RESULTS
Non-cytotoxic concentration of TS extracts (50-100μg/mL) and gallic acid (5μg/mL) inhibited the proliferation of VEGF-stimulated EA.hy 926 and HUVECs. Inhibitory effects of TS extracts and gallic acid on angiogenesis were assessed by VEGF-induced migration/invasion and capillary-like tube formation by EA.hy 926 and HUVECs. Additionally, gelatin zymography assays showed that TS extracts and gallic acid suppressed the activity of metalloproteinase (MMP)-9 and MMP-2 activated by VEGF. In vivo, TS extracts and gallic acid strongly suppressed neovessel formation in the chorioallantoic membrane of chick embryos. Flow cytometry analyses and Western blot demonstrated that treatment with TS extracts and gallic acid induced G(0)/G(1) arrest in VEGF-stimulated EA.hy 926 cells via a reduction in the amounts of cyclin D1, cyclin E, CDK4, hyperphosphorylated retinoblastoma protein (pRb), VEGFR-2, and eNOS.


CONCLUSIONS
These results support an anti-angiogenic activity of Toona sinensis that may contribute critically to its cancer and inflammation chemopreventive potentials.
Department of Cosmeceutics, College of Pharmacy, China Medical University, Taichung, Taiwan.
You-Cheng
YC
Hseu
Ssu-Ching
SC
Chen
Wen-Hsin
WH
Lin
Dong-Zong
DZ
Hung
Ming-Kuem
MK
Lin
Yueh-Hsiung
YH
Kuo
Mei-Tsun
MT
Wang
Hsin-Ju
HJ
Cho
Lai
L
Wang
Hsin-Ling
HL
Yang
D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D029582:Meliaceae / Q000737:chemistry*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A