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Published on: August 3, 2018
Apoptotic activity of doxazosin on prostate stroma in vitro is mediated through an autocrine expression of TGF-beta1
1Department of Urology, Northwestern University Medical School, Chicago, Illinois, USA.
Background:
Doxazosin, an alpha-adrenergic antagonist, has been shown to induce apoptosis in prostatic stromal cells. The mechanism of this apoptotic action by Doxazosin remains undefined. The present study was carried out to demonstrate that the effect of Doxazosin on apoptosis of prostate stromal cells is mediated through an autocrine action of TGF-beta1.
Methods:
Primary cultures of human prostate cells were treated with varying concentrations of Doxazosin (0, 0.1, 1, 10, and 100 microM) for a period up to 3 days. At the end of the 3-day culture, cell numbers were counted. Apoptosis was assessed by a colorimetric terminal deoxyribonucleotide transferase labeling technique. TGF-beta1 was determined by enzyme-linked immunosorbent assay (ELISA).
Results:
Compared to control cultures, cell numbers were significantly decreased as much as 68.4% in cultures treated with 10 microM of Doxazosin after 3 days incubation, while apoptosis increased by 64.7% in cultures treated with the same concentration of Doxazosin after 24 h. This decrease in cell number was reversed when antibody to TGF-beta1 was added to these cultures. Addition of TGF-beta1 (0, 1.0, and 10 ng/mL) to the cultures also decreased the cell numbers. Quantitation of TGF-beta1 in lysates of cells by ELISA revealed that the cells treated with Doxazosin (10 microM) produced as much as 62.5% more TGF-beta1 than in that of untreated cells.
Conclusions:
These results demonstrate that the apoptotic effect of Doxazosin on human prostatic stromal cells is mediated through an autocrine production of TGF-beta1.
Insights
Doxazosin induces apoptosis in prostate cells via TGF-beta1. Blocking TGF-beta1 reversed Doxazosin
Area of Science:
- Cell Biology
- Pharmacology
- Urology
Background:
- Doxazosin, an alpha-adrenergic antagonist, induces apoptosis in prostatic stromal cells.
- The precise mechanism of Doxazosin-induced apoptosis in prostate cells was previously undefined.
- This study investigated the role of transforming growth factor-beta1 (TGF-beta1) in Doxazosin's apoptotic effects.
Purpose of the Study:
- To elucidate the mechanism by which Doxazosin induces apoptosis in human prostate stromal cells.
- To determine if the autocrine action of TGF-beta1 mediates Doxazosin's apoptotic effects.
- To investigate the relationship between Doxazosin treatment, TGF-beta1 production, and apoptosis in prostate cells.
Main Methods:
- Primary human prostate cell cultures were treated with varying Doxazosin concentrations (0-100 microM) for 3 days.
- Apoptosis was quantified using a terminal deoxynucleotidyl transferase labeling technique.
- TGF-beta1 levels were measured by enzyme-linked immunosorbent assay (ELISA).
Main Results:
- Doxazosin (10 microM) significantly decreased prostate cell numbers by 68.4% and increased apoptosis by 64.7%.
- The addition of TGF-beta1 antibody reversed Doxazosin-induced cell number reduction.
- Doxazosin treatment elevated cellular TGF-beta1 production by 62.5%.
Conclusions:
- Doxazosin-induced apoptosis in human prostate stromal cells is mediated by autocrine TGF-beta1 production.
- TGF-beta1 plays a crucial role in the mechanism of Doxazosin's action on prostate cells.
- These findings clarify the molecular pathway of Doxazosin's effects on prostatic stromal cells.
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