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

Abstract

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.

Keywords: apoptosis; doxazosin; epithelial stem cells; prostate.

Fig. 1

Apoptotic and viable cells after incubation with increasing concentrations of doxazosin (20, 50 and 80 µM) measured using flow cytometry (Annexin V-FITC and iodide propidium – IP labeling).