Abstract
OBJECTIVE: To assess the mechanisms of action of phenylbutyrate (PB), an investigational chemotherapeutic agent for prostate cancer (PCa), in apoptosis induction in PCa cell lines in vitro. STUDY DESIGN: We analyzed the differential expression of different apoptosis modulators, Bcl-2, Bax, p53 and Fas, for their potential role in PB-induced apoptosis using relative quantitative flow cytometry (FCM). Both androgen-dependent (LNCaP) and androgen-independent (C-4-2, PC-3-PF and DU145) human PCa cell lines were examined. RESULTS: PB induced apoptosis in PCa cell lines in a dose-dependent manner. Fifty percent apoptosis could be induced by 5-10 mM PB. Bcl-2 was down-regulated 30-75% and the Bax:Bcl-2 ratio elevated in apoptotic PCa cell lines regardless of their androgen dependency or p53 status. FCM revealed a heterogeneous stimulatory effect on the expression of Bax and Bcl-2 in PC3-PF cells at 0.5-2.5 mM PB. In a p53-positive cell line (DU145), p53 was repressed by 70% and Fas elevated sixfold with 10 mM PB. CONCLUSION: Our data show that PB-induced PCa apoptosis is associated with the relative repression of Bcl2 and with up-regulation of Bax and Fas proteins and that this PB- induced apoptosis is independent of p53 and androgen-dependency status of PCa cell lines.
Original language | English (US) |
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Pages (from-to) | 45-54 |
Number of pages | 10 |
Journal | Analytical and Quantitative Cytology and Histology |
Volume | 22 |
Issue number | 1 |
State | Published - Feb 1 2000 |
Keywords
- Apoptosis
- Phenylbutyrates
- Prostate cancer
ASJC Scopus subject areas
- Anatomy
- Histology