Related Experiment Video
Updated: Oct 22, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Alpha 1-adrenoceptor antagonists terazosin and doxazosin induce prostate apoptosis without affecting cell
J K Chon1, A Borkowski, A W Partin
1Division of Urology, University of Maryland School of Medicine, Baltimore, USA.
Purpose:
Recent evidence indicated that an alpha 1 blocker, doxazosin, induces prostate apoptosis in patients with benign prostatic hyperplasia (BPH). In this study, to determine whether this apoptotic response was mediated by alpha 1 adrenoceptor-dependent mechanism or was specific to doxazosin, we examined the effect of another alpha 1 blocker, terazosin, in addition to doxazosin, on the dynamics of prostate cell growth.
Materials And Methods:
Cell proliferation and apoptosis were evaluated in BPH patients, an untreated (control) group (n = 31), and men treated with terazosin (n = 42) and doxazosin (n = 61) for the relief of the obstructive symptoms. Terazosin (1 to 10 mg./day) and doxazosin (2 to 8 mg./day) treatment varied from 1 week to 3 years. Ki-67 immunostaining and the TUNEL assay were used to evaluate the proliferative and apoptotic indices, respectively, in both the epithelial and stromal components of prostate (biopsy and prostatectomy) specimens. The smooth muscle cell content of the prostatic stroma was identified on the basis of smooth muscle alpha-actin immunoreactivity.
Results:
A significant induction of apoptosis was observed in both the prostatic epithelial and stromal cells within the first month of terazosin and doxazosin therapy, as compared with untreated controls (p < 0.05). Furthermore, the marked induction of prostatic stroma apoptosis in response to both alpha 1 adrenoceptor antagonists was paralleled by a significant decrease in the smooth muscle alpha-actin expression. This loss of prostatic smooth muscle cells correlated with morphological stromal regression (as detected by trichrome staining) and BPH symptom improvement. Neither terazosin nor doxazosin therapy resulted in significant changes in prostate cell proliferation.
Conclusions:
These findings demonstrate that alpha-blockers as a class may regulate prostate growth by inducing apoptosis in both the epithelial and stromal cells, with little effect on cell proliferation. Apoptosis-mediated prostate stromal regression appears as a molecular mechanism underlying the therapeutic response to alpha 1 blockade in the treatment of BPH.
Insights
Alpha-blockers like terazosin and doxazosin induce prostate cell apoptosis, leading to stromal regression and symptom improvement in benign prostatic hyperplasia (BPH) patients. This apoptosis-driven mechanism is key to BPH treatment.
Area of Science:
- Urology
- Cell Biology
- Pharmacology
Background:
- Benign prostatic hyperplasia (BPH) is a common condition in aging men.
- Alpha-1 blockers are a standard treatment for BPH symptoms.
- Doxazosin has shown evidence of inducing prostate apoptosis.
Purpose of the Study:
- To investigate if the apoptotic response to alpha-1 blockers is specific to doxazosin or mediated by the alpha-1 adrenoceptor.
- To examine the effect of terazosin, another alpha-1 blocker, on prostate cell growth dynamics.
Main Methods:
- Evaluated cell proliferation and apoptosis in BPH patients using Ki-67 immunostaining and TUNEL assay.
- Compared untreated controls with patients treated with terazosin or doxazosin.
- Assessed epithelial and stromal cell components and smooth muscle alpha-actin immunoreactivity.
Main Results:
- Both terazosin and doxazosin significantly induced apoptosis in prostate epithelial and stromal cells within one month.
- Apoptosis induction correlated with decreased smooth muscle alpha-actin expression and stromal regression.
- Neither drug significantly altered prostate cell proliferation.
Conclusions:
- Alpha-blockers as a class can regulate prostate growth by inducing apoptosis in both epithelial and stromal cells.
- Apoptosis-mediated stromal regression is a likely mechanism for therapeutic response in BPH.
- The observed effects are mediated by alpha-1 adrenoceptor antagonism, not specific to doxazosin.
Related Concept Videos
01:22Adrenergic Antagonists: Pharmacological Actions of ɑ-Receptor Blockers
α1-blockers: These drugs inhibit α1-adrenoceptors on smooth muscle cells, resulting in vasodilation. This vasodilation lowers blood pressure, making α1-blockers valuable in treating hypertension. Additionally, α1-blockers effectively address urinary obstruction...
01:23Antihypertensive Drugs: Vasodilators
01:17Adrenergic Antagonists: Chemistry and Classification of ɑ-Receptor Blockers
Nonselective α-blockers: Nonselective α-blockers contain haloalkylamine or imidazoline moieties. Phenoxybenzamine, with a haloalkylamine...
01:31Adrenergic Receptors: ɑ Subtype
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase C—inositol-1,4,5-trisphosphate...
01:15Antihypertensive Drugs: Thiazide-Class Diuretics
01:30Antihypertensive Drugs: Angiotensin II Receptor Blockers