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Differential mechanisms of bicalutamide-induced apoptosis in prostate cell lines

Prostate Cancer and Prostatic Diseases volume 12, pages 25–33 (2009)Cite this article

A Corrigendum to this article was published on 10 November 2011

Abstract

Bicalutamide is a non-steroidal antiandrogen used in the treatment of prostate cancer. Although widely accepted as an androgen receptor antagonist, the mechanism by which it induces apoptosis remains unclear. Defining exact pathways by which bicalutamide induces its apoptotic effects would help to advance its clinical applications. We aimed to (a) examine the apoptotic effects of bicalutamide at 24 h and (b) comment on the role of the caspases and calpains in mediating bicalutamide-induced apoptosis in androgen-dependent and androgen-independent cells. PWR-1E, PC-3 and DU-145 cells were treated with bicalutamide and assessed for apoptosis by flow cytometry at 24 h. DU-145 cells were used to compare differences between two different metastatic receptor-negative cells and to verify apoptotic induction at 48 h. To delineate a specific pathway of action for bicalutamide, PC-3 and PWR-1E cells were pretreated with specific inhibitors of caspase-dependent (zVAD-FMK) and caspase-independent pathways (calpain 2 inhibitor). Bicalutamide induced apoptosis in androgen-dependent PWR-1E cells via a caspase-dependent and calpain-independent mechanism. In androgen-independent PC-3 cells, bicalutamide also induced apoptosis by mechanisms that were partially inhibited by pan-caspase inhibition but were partially calpain dependent. Understanding into how bicalutamide exerts its effects in androgen-independent cells will yield further insights into the treatment of hormone-refractory disease.

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Acknowledgements

Michael St John Floyd Jr was a British Urological Foundation Scholar during the course of this work.

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  1. UCD School of Medicine and Medical Science, UCD Conway Institute of Biomolecular and Biomedical Research, Mater Misericordiae University Hospital, University College Dublin, Dublin, Ireland

    M St John Floyd Jr, S J Teahan, J M Fitzpatrick & R W G Watson

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  1. M St John Floyd Jr
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  2. S J Teahan
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  3. J M Fitzpatrick
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Correspondence to M St John Floyd Jr.

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St John Floyd, M., Teahan, S., Fitzpatrick, J. et al. Differential mechanisms of bicalutamide-induced apoptosis in prostate cell lines. Prostate Cancer Prostatic Dis 12, 25–33 (2009). https://doi.org/10.1038/pcan.2008.23

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