Cellular prostatic acid phosphatase (cPAcP) serves as a useful biomarker of histone deacetylase (HDAC) inhibitors in prostate cancer cell growth suppression

Persistent Link:
http://hdl.handle.net/10150/610307
Title:
Cellular prostatic acid phosphatase (cPAcP) serves as a useful biomarker of histone deacetylase (HDAC) inhibitors in prostate cancer cell growth suppression
Author:
Chou, Yu-Wei; Lin, Fen-Fen; Muniyan, Sakthivel; Lin, Frank C.; Chen, Ching-Shih; Wang, Jue; Huang, Chao-Cheng; Lin, Ming-Fong
Affiliation:
Tissue 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
Issue Date:
2015
Publisher:
BioMed Central
Citation:
Chou et al. Cell Biosci (2015) 5:38 DOI 10.1186/s13578-015-0033-y
Journal:
Cell & 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/)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
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. 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.
EISSN:
2045-3701
DOI:
10.1186/s13578-015-0033-y
Keywords:
Prostate cancer; Histone deacetylase inhibitor; Cellular prostatic acid phosphatase; Biomarker
Version:
Final published version
Additional Links:
http://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-015-0033-y

Full metadata record

DC FieldValue Language
dc.contributor.authorChou, Yu-Weien
dc.contributor.authorLin, Fen-Fenen
dc.contributor.authorMuniyan, Sakthivelen
dc.contributor.authorLin, Frank C.en
dc.contributor.authorChen, Ching-Shihen
dc.contributor.authorWang, Jueen
dc.contributor.authorHuang, Chao-Chengen
dc.contributor.authorLin, Ming-Fongen
dc.date.accessioned2016-05-20T09:03:48Z-
dc.date.available2016-05-20T09:03:48Z-
dc.date.issued2015en
dc.identifier.citationChou et al. Cell Biosci (2015) 5:38 DOI 10.1186/s13578-015-0033-yen
dc.identifier.doi10.1186/s13578-015-0033-yen
dc.identifier.urihttp://hdl.handle.net/10150/610307-
dc.description.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.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://cellandbioscience.biomedcentral.com/articles/10.1186/s13578-015-0033-yen
dc.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/)en
dc.subjectProstate canceren
dc.subjectHistone deacetylase inhibitoren
dc.subjectCellular prostatic acid phosphataseen
dc.subjectBiomarkeren
dc.titleCellular prostatic acid phosphatase (cPAcP) serves as a useful biomarker of histone deacetylase (HDAC) inhibitors in prostate cancer cell growth suppressionen
dc.typeArticleen
dc.identifier.eissn2045-3701en
dc.contributor.departmentTissue Bank and BioBank, Kaohsiung Chang Gung Memorial Hospitalen
dc.contributor.departmentDepartment of Biochemistry and Molecular Biology, College of Medicine, University of Nebraska Medical Centeren
dc.contributor.departmentDivision of Urology, Department of Surgery, University of Arizona Medical Centeren
dc.contributor.departmentDivision of Medicinal Chemistry and Pharmacology, College of Pharmacy, The Ohio State Universityen
dc.contributor.departmentDivision of Oncology/Hematology, Department of Internal Medicine, University of Nebraska Medical Centeren
dc.contributor.departmentUniversity of Arizona Cancer Center, St. Joseph's Hospital and Medical Centeren
dc.contributor.departmentDepartment of Pathology, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicineen
dc.contributor.departmentEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Centeren
dc.contributor.departmentDepartment of Surgery/Urology, University of Nebraska Medical Centeren
dc.contributor.departmentSchool of Pharmacy, Kaohsiung Medical Universityen
dc.identifier.journalCell & Bioscienceen
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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