Antisense oligonucleotides (oligos) have been employed against prostate cancer models targeting growth-regulatory proteins, and at least one oligo (against bcl-2) has reached clinical trial.
The prostate cancer antigen gene 3 (PCA3) is embedded in an intron of a second gene BMCC1 (Bcl2-/adenovirus E1B nineteen kDa-interacting protein 2 (BNIP-2) and Cdc42GAP homology BCH motif-containing molecule at the carboxyl terminal region 1) which is also upregulated in prostate cancer.
This synergistic therapy was associated with the induction of apoptotic cell death with a decreased Bcl2 to Bax expression ratio and increased expression of cleaved caspase 3 and caspase 9 in the prostate cancer xenograft.
BCL2 mRNA expression in the same collective of prostate cancer tissue samples was associated with higher Gleason score and extracapsular extension of the tumour (pT3).
NEU3 silencing with siRNA in prostate cancer PC-3 and LNCaP cells resulted in increased expression of differentiation markers and in cell apoptosis, but decrease in Bcl-2 as well as a progression-related transcription factor, early growth response gene (EGR-1).
In this study, we aimed our attention on determining the expression of Bcl-2, c-Fos, c-Jun, Ki-67, NF-κB and p53 genes in two prostate cell lines, as the 22Rv1 cell line, a model of aggressive partially androgen-sensitive prostate cancer and the PNT1A cell line, a normal prostate cell line model.
The relation of Bcl-2 overexpression and copy number gains or translocation of the BCL-2 gene in prostate cancer under hormone-naïve conditions is unknown.
A natural BH3-mimetic, small-molecule inhibitor of Bcl-2, (-)-gossypol, shows promise in ongoing phase II and III clinical trials for human prostate cancer.
In this study, we show that sHA is a potent inhibitor of prostate cancer. sHA blocked the proliferation, motility, and invasion of LNCaP, LNCaP-AI, DU145, and LAPC-4 prostate cancer cells, and induced caspase-8-dependent apoptosis associated with downregulation of Bcl-2 and phospho-Bad. sHA inhibited Akt signaling including androgen receptor (AR) phosphorylation, AR activity, nuclear factor κB (NFκB) activation, and VEGF expression.
In addition, BCL2 was also found to be frequently silenced in PCa due to aberrant promoter methylation, thus supporting a future role for apoptosis-targeted therapy in prostate cancer.
Thus, rational targeting of both the Bcl-2 and Mcl-1 mechanisms of apoptosis resistance may be therapeutically advantageous for advanced prostate cancer.
Utility of tissue microarrays for profiling prognostic biomarkers in clinically localized prostate cancer: the expression of BCL-2, E-cadherin, Ki-67 and p53 as predictors of biochemical failure after radical prostatectomy with nested control for clinical and pathological risk factors.