Anti-angiogenic effect of triterpenoidal saponins from Polygala senega.
Senegasaponins [senegin II (1), senegin III (2), senegin IV (3), senegasaponin a (4), and senegasaponin b (5)] from Polygala senega were re-discovered as selective anti-proliferative substances against human umbilical vein endothelial cells (HUVECs). Senegasaponins (1-5) showed anti-proliferative activity against HUVECs with IC(50) values in the range 0.6-6.2 μM, and the selective index was 7-100-fold in comparison with those for several cancer cell lines, while the desacyl mixture of senegasaponins (6) and tenuifolin (7) lost anti-proliferative activity, indicating that the 28-O-glycoside moiety and methoxycinnamoyl group were essential for the HUVEC-selective growth inhibition of senegasaponins. Senegin III (2) inhibited the vascular endothelial growth factor (VEGF)-induced in vitro tubular formation of HUVECs and basic fibroblast growth factor (bFGF)-induced in vivo neovascularization in the mouse Matrigel plug assay. Moreover, senegin III (2) suppressed tumor growth in the ddY mice s.c.-inoculated murine sarcoma S180 cells. The analysis of the action mechanism of senegin III (2) suggested that the induction of pigment epithelium-derived factor (PEDF) would contribute to the anti-angiogenic effects of senegasaponins.
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Masayoshi
M
Arai
Asami
A
Hayashi
Mari
M
Sobou
Shunsuke
S
Ishida
Takashi
T
Kawachi
Naoyuki
N
Kotoku
Motomasa
M
Kobayashi
D000818:Animals; D005260:Female; D006801:Humans; D051379:Mice; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015151:Immunoblotting; D015394:Molecular Structure; D018919:Neovascularization, Physiologic / Q000187:drug effects; D031801:Polygala / Q000737:chemistry; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D045786:Diterpenes, Kaurane
D016222:Fibroblast Growth Factor 2; D012503:Saponins; D014315:Triterpenes; D042461:Vascular Endothelial Growth Factor A; C532370:tenuifolin diterpene; D045786:Diterpenes, Kaurane; C407311:tenuifolic saponin