Ailanthone Inhibits Huh7 Cancer Cell Growth via Cell Cycle Arrest and Apoptosis In Vitro and In Vivo

来自 EBSCO

阅读量：

作者：

Z Zhuo，J Hu，X Yang，M Chen，X Lei，L Deng，N Yao，Q Peng，Z Chen，W Ye

展开

摘要：

While searching for natural anti-hepatocellular carcinoma (HCC) components inAilanthus altissima, we discovered that ailanthone had potent antineoplastic activity against HCC. However, the molecular mechanisms underlying the antitumor effect of ailanthone on HCC have not been examined. In this study, the antitumor activity and the underlying mechanisms of ailanthone were evaluatedin vitroandin vivo. Mechanistic studies showed that ailanthone induced G0/G1-phase cell cycle arrest, as indicated by decreased expression of cyclins and CDKs and increased expression of p21 and p27. Our results demonstrated that ailanthone triggered DNA damage characterized by activation of the ATM/ATR pathway. Moreover, ailanthone-induced cell death was associated with apoptosis, as evidenced by an increased ratio of cells in the subG1phase and by PARP cleavage and caspase activation. Ailanthone-induced apoptosis was mitochondrion-mediated and involved the PI3K/AKT signaling pathway in Huh7 cells.In vivostudies demonstrated that ailanthone inhibited the growth and angiogenesis of tumor xenografts without significant secondary adverse effects, indicating its safety for treating HCC. In conclusion, our study is the first to report the efficacy of ailanthone against Huh7 cells and to elucidate its underlying molecular mechanisms. These findings suggest that ailanthone is a potential agent for the treatment of liver cancer.

展开

关键词：

AILANTHUS altissima CANCER cell growth CELL cycle APOPTOSIS DNA damage CASPASES CLEAVAGE (Embryology)

DOI：

10.1038/srep16185

被引量：

年份：

2015