AR-42 induces apoptosis in human hepatocellular carcinoma cells via HDAC5 inhibition

作者：Zhang, Mingming; Pan, Yida; Dorfman, R. G.; Chen, Zhaogui; Liu, Fuchen; Zhou, Qian; Huang, Shan; Zhang, Jun; Yang, Dongqin^*; Liu, Jie^*

来源：Oncotarget, 2016, 7(16): 22285-22294.

DOI：10.18632/oncotarget.8077

• AR-42
• apoptosis
• hepatocellular carcinoma
• HDAC5
• prognosis

Histone deacetylases (HDACs) play critical roles in apoptosis and contribute to the proliferation of cancer cells. AR-42 is a novel Class I and II HDAC inhibitor that shows cytotoxicity against various human cancer cell lines. The present study aims to identify the target of AR-42 in hepatocellular carcinoma (HCC) as well as evaluate its therapeutic efficacy. We found that HDAC5 was upregulated in HCC tissues compared to adjacent normal tissues, and this was correlated with reduced patient survival. CCK8 and colony-formation assays showed that HDAC5 overexpression promotes proliferation in HCC cell lines. Treatment with AR-42 decreased HCC cell growth and increased caspase-dependent apoptosis, and this was rescued by HDAC5 overexpression. We demonstrated that AR-42 can inhibit the deacetylation activity of HDAC5 and its downstream targets in vitro and in vivo. Taken together, these results demonstrate for the first time that AR-42 targets HDAC5 and induces apoptosis in human hepatocellular carcinoma cells. AR-42 therefore shows potential as a new drug candidate for HCC therapy.

• 出版日期2016-4-19
• 单位安徽医科大学; 中国人民解放军第二军医大学; 南京大学; 复旦大学; 西北大学