Doxazosin, an alpha1-adrenoceptor antagonist, is used for the treatment of benign prostatic hyperplasia (BPH) and hypertension. Alpha-adrenoceptor antagonists also inhibit growth and induce apoptosis in malignant prostatic cells. The apoptotic activity is independent of their capacity to antagonize alpha-adrenoceptors. The effect of doxazosin on the growth of prostate and bladder cancer cell lines was assessed and whether the growth inhibitory effect of doxazosin on prostate cancer cells is serotonin (5-hydroxtryptamine; 5-HT)-dependent was investigated.
Materials and methods: PC3 (androgen-independent prostate cancer) and HT1376 (grade III transitional cell carcinoma) cells were plated. The cells were incubated with doxazosin. After 72 h, cell viability was assessed (crystal violet assay). Studies were also performed after incubating the PC3 cells with 5-HT or 5-HTR1B agonists for a short duration, followed by the addition of doxazosin. Cell viability was assessed at 72 h.
Results: Doxazosin caused a dose-dependent inhibition of PC3 and HT1376 cell growth with a maximum inhibition of 80% (n=12, p < 0.0001) and 91% (n=12, p < 0.0001), respectively, at a concentration of 10(-4)M, at 72 h. Incubation of PC3 cells with 5-HT or 5-HTR1B agonist, followed by addition of doxazosin, increased the percent of viable cells as compared to when the cells were treated with doxazosin alone.
Conclusion: Doxazosin significantly inhibited prostate and bladder cancer cell growth. Furthermore, prior incubation of prostate cancer cells with 5-HT or 5-HTR1B agonist increased cell viability as compared to treatment with doxazosin alone. These findings may be related to the similarity between subtype 1 serotonin and adrenergic receptors. The effect of alpha1-adrenoceptor antagonists on tumour cell growth merits further investigation.
Previous studies showed that serotonin (5-HT) stimulated the proliferation of prostate cancer cells mediated by serotonin receptors 5-HTR1A and 5-HTR1B and serotonin receptors antagonists inhibit proliferation. Thus, serotonin has an important role in prostate tumor progression.
List of Serotonin Receptor Antagonists Drugs:
Terazosin, Doxazosin and Prazosin, but not Tamsulosin, suppress the growth of prostate cancer cells
Terazosin, Doxazosin and Prazosin are derivatives of Quinazolines.
Quinazolines possessing wide spectrum of biological properties like antibacterial, antifungal, anticonvulsant, anti-inflammatory, anti-HIV, anticancer and analgesic activities.
Other Quinazoline-Containing Drugs:
-- Afatinib for treatment of cancers resistant to gefinitib and erlotinib.
-- Erlotinib, an anti-tumor agent.
-- Lapatinib for treatment of advanced-stage or metastatic breast cancer.
-- Gefitinib for treatment of non-small-cell lung carcinoma.