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Doxazosin cytotxic to prostate carcinoma cell lines
Researchers from Turkey report that doxazosin may be a new cytotoxic agent for prostate cancer. Doxazosin killed prostate carcinoma cells in vitro and the effect was synregistic with adriamycin and etoposide.
Dr. Cag Cal and colleagues from Ege University School of Medicine, Izmir, used prostate carcinoma cell lines DU145 and PC-3 to test the possible efficacy of doxazosin in the treatment of prostate cancer. Their paper appears in the April issue of the British Journal of Urology (BJU International).
The investigators found that, "DU145 and PC-3 were sensitive to doxazosin-mediated cytotoxicity...and the maximum cytotoxicity was obtained at 72 hours." In addition, the effect was linearly dose dependent, and more than 50% of cells were killed at concentrations of 60 micromoles/L.
When the researchers combined doxazosin with adriamycin the result was a "significant synergistic cytotoxic activity at subtoxic concentrations of both doxazosin and adriamycin." More than half the cells were killed with concentrations of doxazosin at 40 micromoles/L and adriamycin at 1.7 micromoles/L.
Combining etoposide with doxazosin produced a similar result. The group reports that concentrations of 40 micromoles/L of doxazosin and 1 micromole/L of etoposide were sufficient to kill more than half the cells in both lines.
"Interestingly," say the researchers, "the combination of doxazosin and paclitaxel resulted in antagonistic activity which increased with increasing concentrations of doxazosin and paclitaxel."
"Pharmacological agents such as alpha-1-adrenoceptor antagonists (e.g. doxazosin) can disrupt alpha-1-adrenergic receptor-mediated growth control pathways and may provide a specific therapeutic modality for treating human prostate cancer," the researchers conclude.