Doxazosin: a new cytotoxic agent for prostate cancer?
OBJECTIVE
To determine the sensitivity of drug-resistant prostate cancer cell lines to doxazosin-mediated cell death, and the effects of combining doxazosin and chemotherapeutic agents on these cell lines. Materials and methods The cytotoxic effect of doxazosin was initially evaluated in the prostate carcinoma cell lines DU145 and PC-3. Doxazosin was combined either with adriamycin, etoposide or paclitaxel after its cytotoxic effects were detected in these cell lines. The tetrazolium dye (MTT) assay and trypan blue dye-exclusion tests were used to determine drug-mediated cytotoxicity. Experiments were performed at least three times and representative data are presented.


RESULTS
Both cell lines were sensitive to doxazosin-mediated cytotoxicity and the maximum cytotoxicity was achieved after 72 h. While cell death increased with increasing concentrations of doxazosin, 60 micromol/L doxazosin killed more than half of the cells in these cell lines. The combination of doxazosin with both adriamycin and etoposide resulted in significant synergistic cytotoxic activity at subtoxic concentrations of the drugs. Interestingly, the combination of doxazosin and paclitaxel resulted in antagonistic activity.


CONCLUSIONS
Doxazosin-mediated cytotoxicity in the drug-resistant human prostate carcinoma cell lines was confirmed. Combinations of doxazosin with either 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 treatment of prostate cancer.
Cal
C
C
Department of Urology, Division of Medical Oncology and Division of Haematology, Ege University School of Medicine, Izmir, Turkey. cal@med.ege.edu.tr
Uslu
R
R
Gunaydin
G
G
Ozyurt
C
C
Omay
S B
SB
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D017292:Doxazosin / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured
D005047:Etoposide; D004317:Doxorubicin; D017292:Doxazosin; D017239:Paclitaxel