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

Bajek A, Pokrywka L, Wolski Z, Dębski R, Drewa T - Cent European J Urol (2011)

Bottom Line: Cell viability and apoptosis was estimated with Annexin V-FITC. 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).However, progenitor cells were not susceptible to apoptosis, what can be a reason of treatment failure in BPH patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Tissue Engineering, Nicolaus Copernicus University, Bydgoszcz, Poland.

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.

No MeSH data available.


Related in: MedlinePlus

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).
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Figure 0001: 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).

Mentions: 90 primary co-cultures of CD133(+)/CD133(-) cells and 41 primary cultures containing CD133(+) cells were established. 12 h incubation of CD133(+)/CD133(-) co-cultures with doxazosin resulted in decreasing number of viable cells and significant increase of apoptotic cell number (Fig. 1). High correlation (R = 0.98) between cell number and doxazosin concentration was noticed in CD133(+)/CD133(-) co-cultures group. Correlation between apoptotic cell number and doxazosin concentration in CD133(+)/CD133(-) co-cultures group was high (R = 0.99). There was no significant changes in living and apoptotic cell number in CD133(+) primary cultures after 12 h incubation with doxazosin (Fig. 1).


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

Bajek A, Pokrywka L, Wolski Z, Dębski R, Drewa T - Cent European J Urol (2011)

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).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3921739&req=5

Figure 0001: 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).
Mentions: 90 primary co-cultures of CD133(+)/CD133(-) cells and 41 primary cultures containing CD133(+) cells were established. 12 h incubation of CD133(+)/CD133(-) co-cultures with doxazosin resulted in decreasing number of viable cells and significant increase of apoptotic cell number (Fig. 1). High correlation (R = 0.98) between cell number and doxazosin concentration was noticed in CD133(+)/CD133(-) co-cultures group. Correlation between apoptotic cell number and doxazosin concentration in CD133(+)/CD133(-) co-cultures group was high (R = 0.99). There was no significant changes in living and apoptotic cell number in CD133(+) primary cultures after 12 h incubation with doxazosin (Fig. 1).

Bottom Line: Cell viability and apoptosis was estimated with Annexin V-FITC. 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).However, progenitor cells were not susceptible to apoptosis, what can be a reason of treatment failure in BPH patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Tissue Engineering, Nicolaus Copernicus University, Bydgoszcz, Poland.

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.

No MeSH data available.


Related in: MedlinePlus