A novel approach to targeted therapy for prostate cancer: Combination of BCL-2 and akt inhibitors

Prostate cancer still remains the second rank in cancer-related deaths. The development of novel molecules with low toxicity on healthy tissues and evaluating their synergistic effects will provide considerable guidance to the preparation of effective and safe treatment protocols. In the current study, anticancer activity of ABT-737 and erufosine (ErPC3) alone and in combination, on hormone-independent prostate cancer (PC-3, DU-145) and healthy (PNT-1A) cell lines were evaluated under in vitro conditions. The combination of ABT-737 and ErPC3 displayed a synergistic effect in PC-3 cell lines. DU-145 cell lines exhibited resistance against the combination and no increase in cytotoxicity was observed as compared to ErPC3 alone. ABT-737 and ErPC3 alone and in combination slightly decreased the survival of PNT-1A cells only at the highest concentrations. The results obtained from wound healing, Annexin V apoptotic cell analysis, Western Blot and RT-PCR experiments also seemed to support these findings. According to these results, DU-145 cell line is less sensitive to ABT-737 due to the highly expressed anti-apoptotic Mcl-1 protein. Therefore, ABT-737 and ErPC3 combination can be considered less effective in the prostate cancer cell lines in which Mcl-1 protein is highly expressed. This is the first study in the literature which evaluates in vitro anti-cancer activity of ABT-737 and ErPC3 combination in hormone independent prostate cancer. In line with these in vitro findings, designing and conducting in vivo studies are expected to significantly contribute to the results of the current study and also to provide the basis of clinical trials.