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.