Antiangiogenic Effects of Ziyuglycoside II, a Major Active Compound of Sanguisorba officinalis L.

Ziyuglycoside II, a major bioactive compound of Sanguisorba officinalis L., displays anticancer potential against several human cancer cells. However, little information concerning its antiangiogenic properties and possible mechanisms is available. The aim of this study was to investigate the inhibitory effects of ziyuglycoside II on angiogenesis. Ziyuglycoside II inhibited the proliferation, migration, and tubule formation of human umbilical vein endothelial cells, as well as the number of microvessels growing from the aortic rings. The underlying antiangiogenic mechanism of ziyuglycoside II correlated with blocking vascular endothelial growth factor receptor-2 and the fibroblast growth factor receptor-1 mediated signaling pathway. Moreover, an in vivo Matrigel plug assay in mice showed a significant decrease in vascularization and hemoglobin content in the plugs from ziyuglycoside II-treated mice compared with control mice. Overall, these results suggest that ziyuglycoside II inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects. Copyright © 2017 John Wiley & Sons, Ltd.

Ziyuglycoside II induces caspases-dependent and caspases-independent apoptosis in human colon cancer cells.

The development of chemopreventive approaches using natural products including phytochemicals is a potentially useful cancer treatment. The aims of this study were to examine the apoptotic effects of ziyuglycoside II, a major bioactive compound isolated from Sanguisorba officinalis L., on human colon cancer cells. The anticancer effect of ziyuglycoside II was examined in HCT116 (as p53 normal cells) and SW480 (as p53 mutant cells) colon cancer cells. Ziyuglycoside II treatment decreased HCT116 and SW480 cell proliferation. Cell death following ziyuglycoside II treatment was predominantly apoptosis but not cell cycle arrest. Apoptosis caused by p53 phosphorylation following ziyuglycoside II treatment in HCT116 cells involved activation of caspases, increased expression of BAX, mitochondrial cytochrome c and apoptosis inducing factor (AIF) release, while BCL-2 became down-regulated. In contrast, ziyuglycoside II treated SW480 cells displayed no change in phosphorylated-p53 and activation of caspases. Overall, these results suggest that ziyuglycoside II induces apoptosis through caspase-dependent and caspases-independent apoptosis, which was characterized by decreased expression of BCL-2, mitochondrial targeting, and altered production of ROS and translocation of AIF to the nuclei.