Doxazosin: a new cytotoxic agent for prostate cancer?

Objective To determine the sensitivity of drug-resistant prostate cancer ce ll lines to doxazosin-mediated cell death, and the effects of combining dox azosin and chemotherapeutic agents on these cell lines. Materials and methods The cytotoxic effect of doxazosin was initially evalu ated in the prostate carcinoma cell lines DU145 and PC-3. Doxazosin was com bined either with adriamycin, etoposide or paclitaxel after its cytotoxic e ffects were detected in these cell lines. The letrazolium dye (MTT) assay a nd trypan blue dye-exclusion tests were used to determine drug-mediated cyt otoxicity. Experiments were performed at least three times and representati ve data are presented. Results Both cell lines were sensitive to doxazosin-mediated cytotoxicity a nd the maximum cytotoxicity was achieved after 72 h. While cell death incre ased with increasing concentrations of doxazosin, 60 mu moI/L doxazosin kil led more than half of the cells In these cell lines. The combination of dox azosin with both adriamycin and etoposide resulted in significant synergist ic cytotoxic activity at subtoxic concentrations of the drags. Interestingl y, the combination of doxazosin and paclitaxel resulted in antagonistic act ivity. Conclusion Doxazosin-mediated cytotoxicity in the drug-resistant human pros tate carcinoma cell lines was confirmed. Combinations of doxazosin with eit her adriamycin and etoposide, but not paclitaxel, had synergistic cytotoxic activity in these tumour cell lines. These results suggest that doxazosin could be a new cytotoxic agent, either used alone or combined, in the treat ment of prostate cancer.