title: Droxinostat, a Histone Deacetylase Inhibitor, Induces Apoptosis in Hepatocellular Carcinoma Cell Lines via Activation of the Mitochondrial Pathway and Downregulation of FLIP.
abstract: BACKGROUND
  The current chemotherapeutic outcomes for hepatocellular carcinoma (HCC) are not encouraging, and long-term survival of this patient group remains poor. Recent studies have demonstrated the utility of histone deacetylase inhibitors that can disrupt cell proliferation and survival in HCC management. However, the effects of droxinostat, a type of histone deacetylase inhibitor, on HCC remain to be established.
  
  
  METHODS
  The effects of droxinostat on HCC cell lines SMMC-7721 and HepG2 were investigated. Histone acetylation and apoptosis-modulating proteins were assessed via Western blot. Proliferation was examined with 3-(4, 5 dimetyl-2-thiazolyl)-2, 5-diphenyl 2H-tetrazolium bromide, cell proliferation, and real-time cell viability assays, and apoptosis with flow cytometry.
  
  
  RESULTS
  Droxinostat inhibited proliferation and colony formation of the HCC cell lines examined. Hepatoma cell death was induced through activation of the mitochondrial apoptotic pathway and downregulation of FLIP expression. Droxinostat suppressed histone deacetylase (HDAC) 3 expression and promoted acetylation of histones H3 and H4. Knockdown of HDAC3 induced hepatoma cell apoptosis and histone H3 and H4 acetylation.
  
  
  CONCLUSIONS
  Droxinostat suppresses HDAC3 expression and induces histone acetylation and HCC cell death through activation of the mitochondrial apoptotic pathway and downregulation of FLIP, supporting its potential application in the treatment of HCC.
authors.affiliation: Division of Liver Disease, Lanzhou University Second Hospital, Lanzhou, Gansu, China; Department of Gastroenterology, The First People's Hospital of XianYang City, XianYang, Shaanxi, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Division of Liver Disease, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Li
authors.affiliation: Division of Liver Disease, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Division of Liver Disease, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Division of Liver Disease, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Division of Liver Disease, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
authors.forename: Juanxia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Division of Liver Disease, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Division of Liver Disease, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.affiliation: Division of Liver Disease, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Liver Disease, Lanzhou University Second Hospital, Lanzhou, Gansu, China. Electronic address: zhanglymd@126.com.
authors.forename: Lingyi
authors.initials: L
authors.lastname: Zhang