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Prostate epithelial stem cells are resistant to apoptosis after α1-antagonist treatment. The impact for BPH patients

INTRODUCTION: Induction of apoptosis in prostatic epithelial cells by doxazosin, terazosin and prazosin has been well documented. However, the biochemical pathways of doxazosin action is still unclear. Aforementioned drugs should lead to decrease of prostate volume, although this effect was never ob...

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Autores principales: Bajek, Anna, Pokrywka, Łukasz, Wolski, Zbigniew, Dębski, Robert, Drewa, Tomasz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Polish Urological Association 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921739/
https://www.ncbi.nlm.nih.gov/pubmed/24578906
http://dx.doi.org/10.5173/ceju.2011.04.art15
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author Bajek, Anna
Pokrywka, Łukasz
Wolski, Zbigniew
Dębski, Robert
Drewa, Tomasz
author_facet Bajek, Anna
Pokrywka, Łukasz
Wolski, Zbigniew
Dębski, Robert
Drewa, Tomasz
author_sort Bajek, Anna
collection PubMed
description INTRODUCTION: Induction of apoptosis in prostatic epithelial cells by doxazosin, terazosin and prazosin has been well documented. However, the biochemical pathways of doxazosin action is still unclear. Aforementioned drugs should lead to decrease of prostate volume, although this effect was never observed in patients suffering from BPH after treatment with α1-antagonists. Probably, it is connected with cancer stem cells’ resistance on chemotherapeutic agents. The aim of this study was to compare incidence of apoptosis induced by doxazosin in progenitor and differentiated cells isolated from human prostate epithelium. MATERIAL AND METHODS: For this purpose tissue specimens were obtained from 10 patients suffering from BPH, the primary cultures of prostate epithelium were established and CD133 MicroBeads sorting was prepared. Both, CD133(+)/CD133(-) co-cultures and CD133(+) cells were incubated with different concentration of doxazosin for 12 h. Cell viability and apoptosis was estimated with Annexin V-FITC. RESULTS: 12 h incubation of CD133(+)/CD133(-) co-cultures with doxazosin resulted in increase of apoptotic cells, while in CD133(+) cultures no changes were observed. Correlation between apoptotic cell number and doxazosin concentration in CD133(+)/ CD133(-) co-cultures group was high (R = 0.99). CONCLUSION: Doxazosin induced apoptosis in co-cultures of progenitor and differentiated epithelial cells. However, progenitor cells were not susceptible to apoptosis, what can be a reason of treatment failure in BPH patients.
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spelling pubmed-39217392014-02-27 Prostate epithelial stem cells are resistant to apoptosis after α1-antagonist treatment. The impact for BPH patients Bajek, Anna Pokrywka, Łukasz Wolski, Zbigniew Dębski, Robert Drewa, Tomasz Cent European J Urol Basic Science INTRODUCTION: Induction of apoptosis in prostatic epithelial cells by doxazosin, terazosin and prazosin has been well documented. However, the biochemical pathways of doxazosin action is still unclear. Aforementioned drugs should lead to decrease of prostate volume, although this effect was never observed in patients suffering from BPH after treatment with α1-antagonists. Probably, it is connected with cancer stem cells’ resistance on chemotherapeutic agents. The aim of this study was to compare incidence of apoptosis induced by doxazosin in progenitor and differentiated cells isolated from human prostate epithelium. MATERIAL AND METHODS: For this purpose tissue specimens were obtained from 10 patients suffering from BPH, the primary cultures of prostate epithelium were established and CD133 MicroBeads sorting was prepared. Both, CD133(+)/CD133(-) co-cultures and CD133(+) cells were incubated with different concentration of doxazosin for 12 h. Cell viability and apoptosis was estimated with Annexin V-FITC. RESULTS: 12 h incubation of CD133(+)/CD133(-) co-cultures with doxazosin resulted in increase of apoptotic cells, while in CD133(+) cultures no changes were observed. Correlation between apoptotic cell number and doxazosin concentration in CD133(+)/ CD133(-) co-cultures group was high (R = 0.99). CONCLUSION: Doxazosin induced apoptosis in co-cultures of progenitor and differentiated epithelial cells. However, progenitor cells were not susceptible to apoptosis, what can be a reason of treatment failure in BPH patients. Polish Urological Association 2011-12-09 2011 /pmc/articles/PMC3921739/ /pubmed/24578906 http://dx.doi.org/10.5173/ceju.2011.04.art15 Text en Copyright by Polish Urological Association http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Basic Science
Bajek, Anna
Pokrywka, Łukasz
Wolski, Zbigniew
Dębski, Robert
Drewa, Tomasz
Prostate epithelial stem cells are resistant to apoptosis after α1-antagonist treatment. The impact for BPH patients
title Prostate epithelial stem cells are resistant to apoptosis after α1-antagonist treatment. The impact for BPH patients
title_full Prostate epithelial stem cells are resistant to apoptosis after α1-antagonist treatment. The impact for BPH patients
title_fullStr Prostate epithelial stem cells are resistant to apoptosis after α1-antagonist treatment. The impact for BPH patients
title_full_unstemmed Prostate epithelial stem cells are resistant to apoptosis after α1-antagonist treatment. The impact for BPH patients
title_short Prostate epithelial stem cells are resistant to apoptosis after α1-antagonist treatment. The impact for BPH patients
title_sort prostate epithelial stem cells are resistant to apoptosis after α1-antagonist treatment. the impact for bph patients
topic Basic Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921739/
https://www.ncbi.nlm.nih.gov/pubmed/24578906
http://dx.doi.org/10.5173/ceju.2011.04.art15
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