title: Histone deacetylase inhibitors reduce WB-F344 oval cell viability and migration capability by suppressing AKT/mTOR signaling in vitro.
abstract: Histone deacetylase (HDAC) can blockDNA replication and transcription and altered HDAC expression was associated with tumorigenesis. This study investigated the effects of HDAC inhibitors on hepatic oval cells and aimed to delineate the underlying molecular events. Hepatic oval cells were treated with two different HDAC inhibitors, suberoylanilidehydroxamic acid (SAHA) and trichostatin-A (TSA). Cells were subjected to cell morphology, cell viability, cell cycle, and wound healing assays. The expression of proteins related to both apoptosis and the cell cycle, and proteins of the AKT/mammalian target of rapamycin (mTOR) signaling pathway were analyzed by Western blot. The data showed that HDAC inhibitors reduced oval cell viability and migration capability, and arrested oval cells at the G0/G1 and S phases of the cell cycle, in a dose- and time-dependent manner. HDAC inhibitors altered cell morphology and reduced oval cell viability, and downregulated the expression of PCNA, cyclinD1, c-Myc and Bmi1 proteins, while also suppressing AKT/mTOR and its downstream target activity. In conclusion, this study demonstrates that HDAC inhibitors affect oval cells by suppressing AKT/mTOR signaling.
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Biostatistics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Ronglin
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Dongming
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Du
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: jiaoxingyuan@hotmail.com.
authors.forename: Xingyuan
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: gdtrc@163.com.
authors.forename: Xiaoshun
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002867:Chromones / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage*; D006655:Histone Deacetylases / Q000378:metabolism*; D008297:Male; D009025:Morpholines / Q000008:administration & dosage; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020123:Sirolimus / Q000008:administration & dosage; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D002867:Chromones; D056572:Histone Deacetylase Inhibitors; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D006655:Histone Deacetylases; D020123:Sirolimus
keywords: AKT/mTOR signaling pathway; Apoptosis; Cell proliferation; Histone deacetylase inhibitor; Oval cells; Rapamycin