Histone deacetylase inhibitor valproic acid suppresses the growth and increases the androgen responsiveness of prostate cancer cells

Yu Wei Chou; Nagendra K. Chaturvedi; Shougiang Ouyang; Fen Fen Lin; Dharam Kaushik; Jue Wang; Isaac Kim; Ming-Fong Lin

doi:10.1016/j.canlet.2011.07.015

Histone deacetylase inhibitor valproic acid suppresses the growth and increases the androgen responsiveness of prostate cancer cells

Yu Wei Chou, Nagendra K. Chaturvedi, Shougiang Ouyang, Fen Fen Lin, Dharam Kaushik, Jue Wang, Isaac Kim, Ming-Fong Lin

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

Abstract

We identified the molecular target by histone deacetylase (HDAC) inhibitors for exploring their potential prostate cancer (PCa) therapy. Upon HDAC inhibitors-treatment, LNCaP cell growth was suppressed, correlating with increased cellular prostatic acid phosphatase (cPAcP) expression, an authentic protein tyrosine phosphatase. In those cells, ErbB-2 was dephosphorylated, histone H3/H4 acetylation and methylation increased and cyclin proteins decreased. In PAcP shRNA-transfected C-81 cells, valproic acid (VPA) efficacy of growth suppression was diminished. Further, VPA pre-treatment enhanced androgen responsiveness of C-81, C4-2 and MDA PCa2b-AI cells. Thus, cPAcP expression is involved in growth suppression by HDAC inhibitors in PCa cells, and VPA pre-treatments increase androgen responsiveness.

Original language	English (US)
Pages (from-to)	177-186
Number of pages	10
Journal	Cancer Letters
Volume	311
Issue number	2
DOIs	https://doi.org/10.1016/j.canlet.2011.07.015
State	Published - Dec 8 2011

Keywords

Androgen responsiveness
CPAcP
ErbB-2
HDAC inhibitors
Prostate cancer

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.canlet.2011.07.015

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title = "Histone deacetylase inhibitor valproic acid suppresses the growth and increases the androgen responsiveness of prostate cancer cells",

abstract = "We identified the molecular target by histone deacetylase (HDAC) inhibitors for exploring their potential prostate cancer (PCa) therapy. Upon HDAC inhibitors-treatment, LNCaP cell growth was suppressed, correlating with increased cellular prostatic acid phosphatase (cPAcP) expression, an authentic protein tyrosine phosphatase. In those cells, ErbB-2 was dephosphorylated, histone H3/H4 acetylation and methylation increased and cyclin proteins decreased. In PAcP shRNA-transfected C-81 cells, valproic acid (VPA) efficacy of growth suppression was diminished. Further, VPA pre-treatment enhanced androgen responsiveness of C-81, C4-2 and MDA PCa2b-AI cells. Thus, cPAcP expression is involved in growth suppression by HDAC inhibitors in PCa cells, and VPA pre-treatments increase androgen responsiveness.",

keywords = "Androgen responsiveness, CPAcP, ErbB-2, HDAC inhibitors, Prostate cancer",

author = "Chou, {Yu Wei} and Chaturvedi, {Nagendra K.} and Shougiang Ouyang and Lin, {Fen Fen} and Dharam Kaushik and Jue Wang and Isaac Kim and Ming-Fong Lin",

note = "Funding Information: This study is supported in part by NIH Grant (2R01CA88184), DOD (PC050769 and PC074289) and Nebraska Research Initiative. We thank Dr. Stanislav Zelivianski for his support in the early phase of the reporter gene assay and Drs. David Klinkebiel and Judith Christman for analyzing the methylation status of PAcP promoter.",

year = "2011",

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doi = "10.1016/j.canlet.2011.07.015",

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AU - Chou, Yu Wei

AU - Chaturvedi, Nagendra K.

AU - Ouyang, Shougiang

AU - Lin, Fen Fen

AU - Kaushik, Dharam

AU - Wang, Jue

AU - Kim, Isaac

AU - Lin, Ming-Fong

N1 - Funding Information: This study is supported in part by NIH Grant (2R01CA88184), DOD (PC050769 and PC074289) and Nebraska Research Initiative. We thank Dr. Stanislav Zelivianski for his support in the early phase of the reporter gene assay and Drs. David Klinkebiel and Judith Christman for analyzing the methylation status of PAcP promoter.

PY - 2011/12/8

Y1 - 2011/12/8

N2 - We identified the molecular target by histone deacetylase (HDAC) inhibitors for exploring their potential prostate cancer (PCa) therapy. Upon HDAC inhibitors-treatment, LNCaP cell growth was suppressed, correlating with increased cellular prostatic acid phosphatase (cPAcP) expression, an authentic protein tyrosine phosphatase. In those cells, ErbB-2 was dephosphorylated, histone H3/H4 acetylation and methylation increased and cyclin proteins decreased. In PAcP shRNA-transfected C-81 cells, valproic acid (VPA) efficacy of growth suppression was diminished. Further, VPA pre-treatment enhanced androgen responsiveness of C-81, C4-2 and MDA PCa2b-AI cells. Thus, cPAcP expression is involved in growth suppression by HDAC inhibitors in PCa cells, and VPA pre-treatments increase androgen responsiveness.

AB - We identified the molecular target by histone deacetylase (HDAC) inhibitors for exploring their potential prostate cancer (PCa) therapy. Upon HDAC inhibitors-treatment, LNCaP cell growth was suppressed, correlating with increased cellular prostatic acid phosphatase (cPAcP) expression, an authentic protein tyrosine phosphatase. In those cells, ErbB-2 was dephosphorylated, histone H3/H4 acetylation and methylation increased and cyclin proteins decreased. In PAcP shRNA-transfected C-81 cells, valproic acid (VPA) efficacy of growth suppression was diminished. Further, VPA pre-treatment enhanced androgen responsiveness of C-81, C4-2 and MDA PCa2b-AI cells. Thus, cPAcP expression is involved in growth suppression by HDAC inhibitors in PCa cells, and VPA pre-treatments increase androgen responsiveness.

KW - Androgen responsiveness

KW - CPAcP

KW - ErbB-2

KW - HDAC inhibitors

KW - Prostate cancer

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Histone deacetylase inhibitor valproic acid suppresses the growth and increases the androgen responsiveness of prostate cancer cells

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Keywords

ASJC Scopus subject areas

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