TY - JOUR
T1 - Histone deacetylase inhibitors reduce WB-F344 oval cell viability and migration capability by suppressing AKT/mTOR signaling in vitro
AU - Zhang, Peng
AU - Zhu, Xiaofeng
AU - Wu, Ying
AU - Hu, Ronglin
AU - Li, Dongming
AU - Du, Jun
AU - Jiao, Xingyuan
AU - He, Xiaoshun
N1 - Funding Information:
This study was supported in part by grants from the National Natural Science Foundation of China (# 81270531 and 81071984 ), the Natural Science Foundation of Guangdong Province of China (# 2009B030801371 ), and The Specialized Research fund for the doctoral thesis program of higher education in China (# 20120171110073 ).
Publisher Copyright:
© 2015 Elsevier B.V. All rights reserved.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2016/1/15
Y1 - 2016/1/15
N2 - 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.
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.
KW - AKT/mTOR signaling pathway
KW - Apoptosis
KW - Cell proliferation
KW - Histone deacetylase inhibitor
KW - Oval cells
KW - Rapamycin
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U2 - 10.1016/j.abb.2015.11.004
DO - 10.1016/j.abb.2015.11.004
M3 - Article
C2 - 26558695
AN - SCOPUS:84947062603
VL - 590
SP - 1
EP - 9
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
SN - 0003-9861
ER -