The influence of alpha1-antagonist on the expression pattern of TNF receptor family in primary culture of prostate epithelial cells from BPH patients.
Doxazosin triggers apoptosis via an imprecisely defined receptor mechanism that is related to tumor necrosis factor receptors (TNFRs). The aim of this study was to determine CD95, TNFR-1, TNFR-2, CD40 expression in primary prostate epithelial cultures incubated with doxazosin. Epithelial cultures were cultivated from 10 benign prostate hyperplasia patients. The cells were incubated with 20, 50 and 80 microM of doxazosin. Apoptosis was confirmed by fluorescence microscopy and flow cytometry. The cells were analyzed for expression of FAS, CD40, TNFR-1 and TNFR-2 by flow cytometry. Early apoptotic cells were present in all groups. A positive correlation was noticed between doxazosin dose and TNFR-1-, -2-positive cells. A decrease of CD40-positive cell population was observed in the lowest concentration. A decrease of mean fluorescence intensity signal of CD40 and CD95 was observed in the lowest concentration. Doxazosin-triggered apoptosis was dose-independent. The initiation of apoptosis was a result of receptors 'crosstalk' rather than a single receptor pathway activation. TNF receptor self-assembly process should be checked as a potential mechanism leading to apoptosis after doxazosin treatment.
Drewa
T
T
Department of General, Oncologic and Pediatric Urology, Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland. tomaszdrewa@wp.pl
Wolski
Z
Z
Misterek
B
B
Debski
R
R
Styczynski
J
J
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000368:Aged; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D019013:CD40 Antigens / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D017292:Doxazosin / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D009336:Necrosis; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D019013:CD40 Antigens; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D019014:fas Receptor; D017292:Doxazosin