Induction of Apoptosis by alpha1-Adrenoceptor Antagonists in Benign Prostatic Hyperplasia

Lee, Hyung Il; Kim, Ki Kwon; Lee, Kyung Seop

Abstract

PURPOSE: Recent evidence has indicated that alpha1-adrenoceptor antagonists induce prostate apoptosis in patients with benign prostatic hyperplasia (BPH). In this study, the effects of different alpha1-adrenoceptor antagonists, on the apoptosis and cell proliferation in the prostatic glandular epithelium and stroma of patients with benign prostatic hyperplasia, were evaluated.
MATERIALS AND METHODS
A retrospective analysis was performed on BPH patients for the relief of lower urinary tract symptoms; an untreated (control) group (n=28), and patients treated with terazosin (n=26), doxazosin (n=27) and tamsulosin (n=15) were included. Archival prostate specimens were selected on the basis of availability of previous TURP (transurethral resection of the prostate) specimens. Terazosin, doxazosin and tamsulosin (2-8mg/day) treatment periods ranged from 1 week to 6 years. Ki-67 immunostaining and the TUNEL assay were used to evaluate the proliferative and apoptotic indices for both the epithelial and stromal components of prostate specimens.
RESULTS
A significant induction of apoptosis was observed in patients treated with the alpha1-adrenoceptor antagonists, terazosin and doxazosin, compared with the untreated control group (p<0.01). However, the alpha1A-adrenoceptor antagonist, tamsulosin, resulted in no significant apoptosis. Terazosin, doxazosin and tamsulosin therapy resulted in no significant changes in the prostate cell proliferation (p>0.05).
CONCLUSIONS
Our findings demonstrated that alpha1-adrenoreceptor antagonists may regulate the prostate growth, by inducing apoptosis in both the epithelial and stromal cells, with little effect on the cell proliferation. Apoptosis-mediated prostate stromal regression appears as an additional molecular mechanism underlying the therapeutic response to alpha1-adrenoceptor antagonists in the treatment of BPH.