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Dirty deeds done dirt cheap: sensitization of prostate cancer cells to abiraterone treatment using hydroxylated polychlorinated biphenyls

  • Gabriel Daragan
  • Jenny Hoffmann
  • Theresa Vasko
  • Alexander Mustea
  • Martin Burchardt
  • Thomas Kraus
  • Matthias B. Stope
  • Patrick ZieglerEmail author
SHORT REPORT

Summary

Effective targeting of androgen biosynthesis by the 17α-hydroxylase/17,20-lyase inhibitor abiraterone prolongs survival in a variety of prostate cancer patients. However, resistance to abiraterone treatment occurs frequently and the development of new drugs supporting or complementing abiraterone therapy is urgently needed. We recently reported antiproliferative and proapoptotic effects of hydroxylated polychlorinated biphenyls (PCBs) on various blood cell lines in vitro. Here we report the biological evaluation of the PCB28 derived OH-metabolites 3-OHCB28 or 3′-OHCB28 in prostate cancer cells. Depending on concentration, both metabolites inhibit the growth of PC3 cells, a cell line representing later stages of advanced prostate cancer. In addition 3′-OHCB28 reduced the necessary concentration of abiraterone required for the inhibition of PC3 cells by a factor of 4. Western blot analysis of cytoprotective heatshock proteins (HSP) implicated a significant reduction of HSP27 expression by 3′-OHCB28 in PC3 cells. Given the known HSP27 suppressive role of abiraterone, our results therefore suggest, that that the pharmacological interaction between abiraterone and 3′-OHCB28 in PC3 cells could be produced by the combined effect of both substances on the expression of HSPs, especially the expression of HSP27. Including the known dose response linkages and pharmacokinetic characteristics of the OH-metabolites described here, we conclude, that the use of hydroxylated PCBs can be supportive for the anti-proliferative treatment of prostate cancer and merits further investigation.

Keywords

Polychlorinated biphenyls Prostate cancer cells Abiraterone 

Notes

Funding

This work was supported by a START-grant (AZ 14/16) of the Faculty of Medicine RWTH Aachen University to PZ.

Compliance with ethical standards

Conflict of interest

All the authors declare that they have no conflict of interest.

Ethical approval

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

Informed consent

For this type of study, formal consent is not required

Supplementary material

10637_2019_833_MOESM1_ESM.pdf (148 kb)
Supplemental Figure 1 3-OHCB28 and 3′-OHCB28 modulate heatshock protein expression in PC3 cells. A + B) Western blot analysis of relative expression of HSP40, HSP60, HSP90α and the Hsp70-Hsp90 organizing protein (HOP) in the presence of 20 μM OHCB28 or 3′-OHCB28 at the indicated timepoints. Data were standardized to vehicle treated cells (control = 1.0) with glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as loading control. Error bars indicate ± SD. *p ≤ 0.05, **p ≤ 0.01 ***p ≤ 0.001, as determined by Student’s t test. (PDF 147 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Gabriel Daragan
    • 1
  • Jenny Hoffmann
    • 2
  • Theresa Vasko
    • 2
  • Alexander Mustea
    • 3
  • Martin Burchardt
    • 1
  • Thomas Kraus
    • 2
  • Matthias B. Stope
    • 1
  • Patrick Ziegler
    • 2
    Email author
  1. 1.Department of UrologyUniversity Medicine GreifswaldGreifswaldGermany
  2. 2.Institute for Occupational, Social and Environmental MedicineRWTH Aachen UniversityAachenGermany
  3. 3.Department of Gynaecology and ObstetricsUniversity Medicine GreifswaldGreifswaldGermany

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