title: Prostate epithelial stem cells are resistant to apoptosis after α1-antagonist treatment. The impact for BPH patients.
abstract: BACKGROUND
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Tissue Engineering, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Bajek
authors.affiliation: Department of General, Oncological and Pediatric Urology, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Pokrywka
authors.affiliation: Department of General, Oncological and Pediatric Urology, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Wolski
authors.affiliation: Department of Pediatric Hematology and Oncology, Nicolaus Copernicus University, Bydgoszcz, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Dębski
authors.affiliation: Department of Tissue Engineering, Nicolaus Copernicus University, Bydgoszcz, Poland ; Department of Urology, Institute of Oncology, Bydgoszcz, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Drewa
keywords: apoptosis; doxazosin; epithelial stem cells; prostate