World Journal of Urology

, Volume 37, Issue 2, pp 343–349 | Cite as

The BET-inhibitor PFI-1 diminishes AR/AR-V7 signaling in prostate cancer cells

  • Marie C. Hupe
  • M. Raschid Hoda
  • Friedemann Zengerling
  • Sven Perner
  • Axel S. Merseburger
  • Marcus V. CronauerEmail author
Original Article



The bromodomain and extra-terminal (BET) family of proteins provides a scaffolding platform for the recruitment and tethering of transcription factors to acetylated chromatin, thereby modulating gene expression. In this study, we evaluated the efficacy of the BET-inhibitor PFI-1 to diminish AR/AR-V7 signaling and proliferation in castration-resistant prostate cancer cells.


Prostate-specific antigen and androgen receptor (AR) protein were quantified by means of two commercial ELISAs. Transactivation of the AR, AR-V7 and Q641X was determined by reporter gene assays. Cell proliferation was measured using a colorimetric MTT-assay.


PFI-1 dose-dependently inhibited transactivation of full-length AR (non- mutated, i.e., wild-type or point-mutated/promiscuous forms) without affecting their cellular protein levels. Moreover, PFI-1 was active against C-terminally truncated constitutively active ARs like AR-V7 and Q641X. Prostate cancer cells exhibiting a transcriptionally active AR-signaling complex (LNCaP, 22Rv1) were more susceptible to the growth-inhibitory effects than the AR-negative PC-3 cells.


The quinazolinone PFI-1 is a highly efficient inhibitor of AR-signaling-competent prostate cancer cells in vitro. PFI-1 could serve as a lead compound for the development of new therapeutics able to block AR/AR-V7 signaling in advanced prostate cancer.


BET inhibitor BRD4 Androgen receptor AR-V7 



The authors wish to thank Beate Godau and Christine Marschke for expert technical assistance.

Author contributions

MCH: data collection and protocol development; MHR: data collection; FZ: data collection; SP: data analysis; ASM: data analysis and manuscript writing/editing; MVC: project development, data analysis, and manuscript writing.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

345_2018_2382_MOESM1_ESM.pdf (6 kb)
Supplementary material 1 (PDF 5 kb)
345_2018_2382_MOESM2_ESM.pdf (182 kb)
Supplementary material 2 (PDF 182 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Marie C. Hupe
    • 1
  • M. Raschid Hoda
    • 1
  • Friedemann Zengerling
    • 2
  • Sven Perner
    • 3
  • Axel S. Merseburger
    • 1
  • Marcus V. Cronauer
    • 1
    Email author
  1. 1.Department of UrologyUniversity Hospital Schleswig-HolsteinLübeckGermany
  2. 2.Department of UrologyUniversity of UlmUlmGermany
  3. 3.Pathology of the University Hospital Schleswig-Holstein, Campus Lübeck and Research Center Borstel, Leibniz Center for Medicine and BiosciencesBorstelGermany

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