Collectively, our findings demonstrate that FN exerts the anticarcinogenic effect on prostate cancer in vitro, in which the underlying mechanisms are associated with enhancing the Bax/Bcl-2 ratios and regulating the p38/Akt pathway, thus triggering apoptosis in tumor cells.
We found a significant increase in both mRNA expression of the anti-apoptotic Bcl-2 gene and VDAC1 gene in prostate cancer tissue in comparison with their normal counterparts.
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).
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.
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 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.
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.
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 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.
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 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.
PCPH/ENTPD5 expression confers to prostate cancer cells resistance against cisplatin-induced apoptosis through protein kinase Calpha-mediated Bcl-2 stabilization.