title: Cytochrome P450 17A1 Inhibitor Abiraterone Acetate Counteracts the Heat Shock Protein 27's Cell Survival Properties in Prostate Cancer Cells.
abstract: BACKGROUND
  Inhibition of androgen synthesis by abiraterone acetate (AA) entails enhanced overall survival rates and clinical benefit for patients with locally advanced and metastasized prostate cancer (PC). The expression of heat shock protein 27 (HSP27) is generally associated with cytoprotection and was demonstrated to mediate chemoresistance under cytostatic therapy, for instance, docetaxel treatment. In this study, we investigated the impact of AA treatment on HSP27 expression and PC cell growth.
  
  
  METHODS
  HSP27 expression levels in docetaxel and AA-treated PC cell lines LNCaP and PC-3 were determined by SDS PAGE and Western blot analysis. Proliferation assays were performed using a CASY Cell Counter and Analyzer Model TT (Roche Applied Science).
  
  
  RESULTS
  Despite significantly increased HSP27 expression in PC cells incubated with docetaxel, Western blot analysis implicated a significant reduction of the cytoprotective HSP27 in AA-treated PC cells. Notably, HSP27 stably overexpressed in PC-3-HSP27 cells did not appear as an HSP27-mediated proliferation benefit in the presence of AA as shown in docetaxel incubation studies.
  
  
  CONCLUSIONS
  In contrast to repeatedly demonstrated HSP27-driven chemoresistance related to chemotherapeutics, our results may constitute a broader molecular mode of action of AA chemotherapy. AA efficacy may exert an HSP27 suppressive role that goes beyond the primarily assumed inhibition of androgen biosynthesis.
authors.affiliation: Department of Urology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Weiss
authors.forename: Hannes
authors.initials: H
authors.lastname: Ahrend
authors.forename: Hannah
authors.initials: H
authors.lastname: Grossebrummel
authors.forename: Patrick
authors.initials: P
authors.lastname: Ziegler
authors.forename: Lars-Ove
authors.initials: LO
authors.lastname: Brandenburg
authors.forename: Reinhard
authors.initials: R
authors.lastname: Walther
authors.forename: Uwe
authors.initials: U
authors.lastname: Zimmermann
authors.forename: Martin
authors.initials: M
authors.lastname: Burchardt
authors.forename: Matthias B
authors.initials: MB
authors.lastname: Stope
mesh_terms: D000069501:Abiraterone Acetate / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000494:pharmacology*; D055551:HSP27 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D055551:HSP27 Heat-Shock Proteins; D000069501:Abiraterone Acetate