PMID- 26558695 OWN - NLM STAT- MEDLINE DCOM- 20160602 LR - 20220331 IS - 1096-0384 (Electronic) IS - 0003-9861 (Linking) VI - 590 DP - 2016 Jan 15 TI - Histone deacetylase inhibitors reduce WB-F344 oval cell viability and migration capability by suppressing AKT/mTOR signaling in vitro. PG - 1-9 LID - S0003-9861(15)30097-7 [pii] LID - 10.1016/j.abb.2015.11.004 [doi] AB - 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. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Zhang, Peng AU - Zhang P AD - Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. FAU - Zhu, Xiaofeng AU - Zhu X AD - Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. FAU - Wu, Ying AU - Wu Y AD - Department of Biostatistics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. FAU - Hu, Ronglin AU - Hu R AD - Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. FAU - Li, Dongming AU - Li D AD - Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. FAU - Du, Jun AU - Du J AD - Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China. FAU - Jiao, Xingyuan AU - Jiao X AD - Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: jiaoxingyuan@hotmail.com. FAU - He, Xiaoshun AU - He X AD - Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: gdtrc@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151110 PL - United States TA - Arch Biochem Biophys JT - Archives of biochemistry and biophysics JID - 0372430 RN - 0 (Chromones) RN - 0 (Histone Deacetylase Inhibitors) RN - 0 (Morpholines) RN - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.5.1.98 (Histone Deacetylases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Animals MH - Apoptosis/drug effects/physiology MH - Cell Line MH - Cell Movement/drug effects/physiology MH - Cell Survival/drug effects/*physiology MH - Chromones/administration & dosage MH - Dose-Response Relationship, Drug MH - Down-Regulation/drug effects/physiology MH - Hepatocytes/cytology/drug effects/*physiology MH - Histone Deacetylase Inhibitors/*administration & dosage MH - Histone Deacetylases/*metabolism MH - Male MH - Morpholines/administration & dosage MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Rats, Inbred F344 MH - Signal Transduction/drug effects/physiology MH - Sirolimus/administration & dosage MH - TOR Serine-Threonine Kinases/*metabolism MH - Treatment Outcome OTO - NOTNLM OT - AKT/mTOR signaling pathway OT - Apoptosis OT - Cell proliferation OT - Histone deacetylase inhibitor OT - Oval cells OT - Rapamycin EDAT- 2015/11/13 06:00 MHDA- 2016/06/03 06:00 CRDT- 2015/11/13 06:00 PHST- 2015/03/25 00:00 [received] PHST- 2015/11/03 00:00 [revised] PHST- 2015/11/04 00:00 [accepted] PHST- 2015/11/13 06:00 [entrez] PHST- 2015/11/13 06:00 [pubmed] PHST- 2016/06/03 06:00 [medline] AID - S0003-9861(15)30097-7 [pii] AID - 10.1016/j.abb.2015.11.004 [doi] PST - ppublish SO - Arch Biochem Biophys. 2016 Jan 15;590:1-9. doi: 10.1016/j.abb.2015.11.004. Epub 2015 Nov 10.