Inhibition of telomerase potentiates enzalutamide efficiency of androgen-sensitive human prostate cancer cells

Purpose: Androgen deprivation therapy (ADT) is one of the main strategies to treat prostate cancer (PCa) at various stages of its development. Androgen receptor (AR) antagonists such as enzalutamide are mainstay treatments for castration-sensitive prostate cancer. Though, a majority of patients initially respond to ADT, most will eventually progress to castrate-resistant, due to the development of different mutations on the AR. PCa cells express high telomerase activity, and there is a correlation between the total activity of telomerase and the Gleason score. Therefore, we hypothesized that the combination of enzalutamide plus a telomerase inhibitor could be more effective than enzalutamide alone in decreasing cell survival. Methods: In this study MTT test, RT-qPCR and image-based cytometry were used to investigate cell viability, apoptosis and cell cycle progression of androgen-responsive human prostate cancer LNCaP cells. The cells were treated with 5 mu M enzalutamide and 40 mu M telomerase inhibitor BIBR 1532, or with their combinations for 72 hrs. Results: Enzalutamide and BIBR 1532 alone inhibited cell proliferation in a dose-dependent manner. The combinations of the two agents could synergistically induce apoptotic and necrotic cell death. Either inhibition of telomerase by BIBR 1532 or AR blockages by enzalutamide decreased prostate-specific antigen (PSA) and the catalytic component of telomerase, hTERT, expression. Conclusion: These results suggest that telomerase inhibition therapy may contribute to the efficacy of enzalutamide in the androgen-sensitive PCa model.