2. Academic Validation
  3. AR-42 induces apoptosis in human hepatocellular carcinoma cells via HDAC5 inhibition

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

  • Oncotarget. 2016 Apr 19;7(16):22285-94. doi: 10.18632/oncotarget.8077.
Mingming Zhang 1,  Yida Pan 1,  Robert G Dorfman 2,  Zhaogui Chen 3,  Fuchen Liu 4,  Qian Zhou 5,  Shan Huang 6,  Jun Zhang 1,  Dongqin Yang 1,  Jie Liu 1 7
Affiliations

Affiliations

  • 1 Department of Digestive Diseases of Huashan Hospital, Fudan University, Shanghai, China.
  • 2 Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
  • 3 Department of Gastroenterology, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
  • 4 Department of Hepatobiliary Surgery, The Eastern Hepatobiliary Surgery Hospital of Second Military Medical University, Shanghai, China.
  • 5 School of Life Sciences, Fudan University, Shanghai, China.
  • 6 Department of Pathology, The Second Hospital of Anhui Medical University, Anhui Medical University, Hefei, China.
  • 7 Collaborative Innovation Center of Genetics and Development, Institutes of Biomedical Sciences and Department of Immunology, Shanghai Medical School, Fudan University, Shanghai, China.
PMID: 26993777 DOI: 10.18632/oncotarget.8077
Abstract

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.

Keywords

AR-42; HDAC5; apoptosis; hepatocellular carcinoma; prognosis.

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