title: Cellular prostatic acid phosphatase (cPAcP) serves as a useful biomarker of histone deacetylase (HDAC) inhibitors in prostate cancer cell growth suppression.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Tissue Bank and BioBank, Kaohsiung Chang Gung Memorial Hospital, No. 123, Da-Pi Road, Niao-Song District, Kaohsiung, 833 Taiwan, ROC ; Department of Biochemistry and Molecular Biology, College of Medicine, 985870 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE 68198-5870 USA.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Chou
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, 985870 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE 68198-5870 USA.
authors.forename: Fen-Fen
authors.initials: FF
authors.lastname: Lin
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, 985870 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE 68198-5870 USA.
authors.forename: Sakthivel
authors.initials: S
authors.lastname: Muniyan
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, 985870 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE 68198-5870 USA ; Division of Urology, Department of Surgery, University of Arizona Medical Center, Tucson, AZ USA.
authors.forename: Frank C
authors.initials: FC
authors.lastname: Lin
authors.affiliation: Division of Medicinal Chemistry and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH USA.
authors.forename: Ching-Shih
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Division of Oncology/Hematology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE USA ; University of Arizona Cancer Center, St. Joseph's Hospital and Medical Center, Phoenix, AZ USA.
authors.forename: Jue
authors.initials: J
authors.lastname: Wang
authors.affiliation: Tissue Bank and BioBank, Kaohsiung Chang Gung Memorial Hospital, No. 123, Da-Pi Road, Niao-Song District, Kaohsiung, 833 Taiwan, ROC ; Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.
authors.forename: Chao-Cheng
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, 985870 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE 68198-5870 USA ; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE USA ; Department of Surgery/Urology, University of Nebraska Medical Center, Omaha, NE USA ; School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
authors.forename: Ming-Fong
authors.initials: MF
authors.lastname: Lin
keywords: Biomarker; Cellular prostatic acid phosphatase; Histone deacetylase inhibitor; Prostate cancer