Cellular prostatic acid phosphatase (cPAcP) serves as a useful biomarker of histone deacetylase (HDAC) inhibitors in prostate cancer cell growth suppression
Lin, Frank C.
AffiliationTissue Bank and BioBank, Kaohsiung Chang Gung Memorial Hospital
Department of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Center
Division of Urology, Department of Surgery, University of Arizona Medical Center
Division of Medicinal Chemistry and Pharmacology, College of Pharmacy, The Ohio State University
Division of Oncology/Hematology, Department of Internal Medicine, University of Nebraska Medical Center
University of Arizona Cancer Center, St. Joseph's Hospital and Medical Center
Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center
Department of Surgery/Urology, University of Nebraska Medical Center
School of Pharmacy, Kaohsiung Medical University
MetadataShow full item record
CitationChou et al. Cell Biosci (2015) 5:38 DOI 10.1186/s13578-015-0033-y
JournalCell & Bioscience
Rights© 2015 Chou et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)
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AbstractBACKGROUND: Prostate cancer (PCa) is the most commonly diagnosed solid tumor and the second leading cancer death in the United States, and also one of the major cancer-related deaths in Chinese. Androgen deprivation therapy (ADT) is the first line treatment for metastatic PCa. PCa ultimately relapses with subsequent ADT treatment failure and becomes castrate-resistant (CR). It is important to develop effective therapies with a surrogate marker towards CR PCa. METHOD: Histone deacetylase (HDAC) inhibitors were examined to determine their effects in androgen receptor (AR)/ cellular prostatic acid phosphatase (cPAcP)-positive PCa cells, including LNCaP C-33, C-81, C4-2 and C4-2B and MDA PCa2b androgen-sensitive and androgen-independent cells, and AR/cPAcP-negative PCa cells, including PC-3 and DU 145 cells. Cell growth was determined by cell number counting. Western blot analyses were carried out to determine AR, cPAcP and PSA protein levels. RESULTS: cPAcP protein level was increased by HDAC inhibitor treatment. Valproic acid, a HDAC inhibitor, suppressed the growth of AR/cPAcP-positive PCa cells by over 50% in steroid-reduced conditions, higher than on AR/cPAcP-negative PCa cells. Further, HDAC inhibitor pretreatments increased androgen responsiveness as demonstrated by PSA protein level quantitation. CONCLUSION: Our results clearly demonstrate that HDAC inhibitors can induce cPAcP protein level, increase androgen responsiveness, and exhibit higher inhibitory activities on AR/cPAcP-positive PCa cells than on AR/cPAcP-negative PCa cells. Upon HDAC inhibitor pretreatment, PSA level was greatly elevated by androgens. This data indicates the potential clinical importance of cPAcP serving as a useful biomarker in the identification of PCa patient sub-population suitable for HDAC inhibitor treatment.
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