Abstract
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Phytochemicals are important candidates for developing anticancer agents. Ziyuglycoside II is a major active compound of Sanguisorba officinalis, which exhibits antiproliferation activity in several cancers; however, its action in HCC remains unknown. In this study, we investigated the antitumor activity of ziyuglycoside II against HCC and explored the potential mechanisms. We found that ziyuglycoside II exerts significant inhibitory effects on the viability and clonogenic activity of HCC cells. The proliferation repression mediated by ziyuglycoside II was mainly due to increased apoptosis and reactive oxygen species accumulation, as well as a G0/G1 phase cell-cycle arrest. Additionally, ziyuglycoside II markedly impaired HCC cell migration and invasion, two important steps during metastasis, and these suppressive effects may be attributed to the downregulation of matrix metalloproteinases MMP2 and MMP9 expression. Moreover, ziyuglycoside II blocked the epidermal growth factor receptor/nuclear factor kappa-B (EGFR/NF-kB) signaling, which may contribute to its anticancer activity. Taken together, our findings reveal antiproliferative and antimetastasis activities of ziyuglycoside II in HCC cells, implying that ziyuglycoside II might be a promising candidate for the development of novel anti-HCC drugs.