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

Abstract

While searching for natural anti-hepatocellular carcinoma (HCC) components in Ailanthus 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 evaluated in vitro and in 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 subG1 phase and by PARP cleavage and caspase activation. Ailanthone-induced apoptosis was mitochondrion-mediated and involved the PI3K/AKT signaling pathway in Huh7 cells. In vivo studies 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.

• Authors: Zhenjian Zhuo, Jianyang Hu, Xiaolin Yang, Minfen Chen, Xueping Lei, Lijuan Deng, Nan Yao, Qunlong Peng, Zhesheng Chen, Wencai Ye, Dongmei Zhang
• Journal: Scientific reports (Sci Rep) Vol. 5 Pg. 16185 (Nov 03 2015) ISSN: 2045-2322 [Electronic] England
• PMID: 26525771 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• Cyclin-Dependent Kinase Inhibitor p21
• Quassins
• Cyclin-Dependent Kinase Inhibitor p27
• ailanthone
• Phosphatidylinositol 3-Kinases
• Proto-Oncogene Proteins c-akt
• Cyclin-Dependent Kinases
• Caspases

Topics

• Ailanthus (chemistry, metabolism)
• Animals
• Antineoplastic Agents, Phytogenic (chemistry, pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Caspases (metabolism)
• Cell Line, Tumor
• Cyclin-Dependent Kinase Inhibitor p21 (metabolism)
• Cyclin-Dependent Kinase Inhibitor p27 (metabolism)
• Cyclin-Dependent Kinases (metabolism)
• DNA Damage (drug effects)
• G1 Phase Cell Cycle Checkpoints (drug effects)
• Hep G2 Cells
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Quassins (chemistry, pharmacology, therapeutic use)
• Signal Transduction (drug effects)