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


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.


Polychlorinated biphenyls Prostate cancer cells Abiraterone 



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)


  1. 1.
    Ziegler S, Schettgen T, Beier F, Wilop S, Quinete N, Esser A, Masouleh BK, Ferreira MSV, Vankann L, Uciechowski P, Rink L, Kraus T, Brümmendorf TH, Ziegler P (2017) Accelerated telomere shortening in peripheral blood lymphocytes after occupational polychlorinated biphenyls exposure. Arch Toxicol 91:289–300. CrossRefGoogle Scholar
  2. 2.
    Vasko T, Hoffmann J, Gostek S, Schettgen T, Quinete N, Preisinger C, Kraus T, Ziegler P (2018) Telomerase gene expression bioassays indicate metabolic activation of genotoxic lower chlorinated polychlorinated biphenyls. Sci Rep 8:16903. CrossRefGoogle Scholar
  3. 3.
    Kimbrough RD (1987) Human health effects of polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs). Annu Rev Pharmacol Toxicol 27:87–111. CrossRefGoogle Scholar
  4. 4.
    Lauby-Secretan B, Loomis D, Grosse Y, el Ghissassi F, Bouvard V, Benbrahim-Tallaa L, Guha N, Baan R, Mattock H, Straif K, WHO International Agency for Research on Cancer (2013) Carcinogenicity of polychlorinated biphenyls and polybrominated biphenyls. The Lancet Oncology 14:287–288. CrossRefGoogle Scholar
  5. 5.
    Grimm FA, Hu D, Kania-Korwel I, Lehmler HJ, Ludewig G, Hornbuckle KC, Duffel MW, Bergman Å, Robertson LW (2015) Metabolism and metabolites of polychlorinated biphenyls. Crit Rev Toxicol 45:245–272. CrossRefGoogle Scholar
  6. 6.
    Saupe M, Rauschenberger L, Preuß M, Oswald S, Fussek S, Zimmermann U, Walther R, Knabbe C, Burchardt M, Stope MB (2015) Differential expression of the multidrug resistance 1 (MDR1) protein in prostate cancer cells is independent from anticancer drug treatment and Y box binding protein 1 (YB-1) activity. World J Urol 33:1481–1486. CrossRefGoogle Scholar
  7. 7.
    Grossebrummel H et al (2016) Cytochrome P450 17A1 inhibitor abiraterone attenuates cellular growth of prostate cancer cells independently from androgen receptor signaling by modulation of oncogenic and apoptotic pathways. Int J Oncol 48:793–800. CrossRefGoogle Scholar
  8. 8.
    Weiss M, Ahrend H, Grossebrummel H, Ziegler P, Brandenburg LO, Walther R, Zimmermann U, Burchardt M, Stope MB (2016) Cytochrome P450 17A1 inhibitor Abiraterone acetate counteracts the heat shock protein 27’s cell survival properties in prostate Cancer cells. Urol Int 97:112–117. CrossRefGoogle Scholar
  9. 9.
    AnvariFar H, Amirkolaie AK, Jalali AM, Miandare HK, Sayed AH, Üçüncü Sİ, Ouraji H, Ceci M, Romano N (2018) Environmental pollution and toxic substances: cellular apoptosis as a key parameter in a sensible model like fish. Aquatic toxicology (Amsterdam, Netherlands) 204:144–159. CrossRefGoogle Scholar
  10. 10.
    Becker MM, Gamble W (1982) Determination of the binding of 2,4,5,2′,4′,5′-hexachlorobiphenyl by low density lipoprotein and bovine serum albumin. J Toxicol Environ Health 9:225–234. CrossRefGoogle Scholar
  11. 11.
    Ljunggren SA, Helmfrid I, Salihovic S, van Bavel B, Wingren G, Lindahl M, Karlsson H (2014) Persistent organic pollutants distribution in lipoprotein fractions in relation to cardiovascular disease and cancer. Environ Int 65:93–99. CrossRefGoogle Scholar
  12. 12.
    Purkey HE, Palaninathan SK, Kent KC, Smith C, Safe SH, Sacchettini JC, Kelly JW (2004) Hydroxylated polychlorinated biphenyls selectively bind transthyretin in blood and inhibit amyloidogenesis: rationalizing rodent PCB toxicity. Chem Biol 11:1719–1728. CrossRefGoogle Scholar
  13. 13.
    Lans MC, Klasson-Wehler E, Willemsen M, Meussen E, Safe S, Brouwer A (1993) Structure-dependent, competitive interaction of hydroxy-polychlorobiphenyls, −dibenzo-p-dioxins and -dibenzofurans with human transthyretin. Chem Biol Interact 88:7–21CrossRefGoogle Scholar
  14. 14.
    Quinete N, Esser A, Kraus T, Schettgen T (2017) PCB 28 metabolites elimination kinetics in human plasma on a real case scenario: study of hydroxylated polychlorinated biphenyl (OH-PCB) metabolites of PCB 28 in a highly exposed German cohort. Toxicol Lett 276:100–107. CrossRefGoogle Scholar

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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