An antisense oligonucleotide to cIAP-1 sensitizes prostate cancer cells to fas and TNFalpha mediated apoptosis

BACKGROUND: The inhibitors of apoptosis (IAP) proteins are a family of structurally homologous caspase inhibitors. We synthesized an antisense oligonucleotide (AO) to target a region within the BIR domain of cIAP-1 and examined its ability to facilitate apoptosis in prostate cancer cells. METHODS: We transfected the IAP AO into PC3 and DU145 cells and determined alterations in IAP expression using Western blotting. Apoptosis and viability were assessed using propidium iodide (PI) DNA incorporation with flow cytometry. Pacitaxel, caffeic acid phenethyl ester (CAPE), Fas antibody, and TNFalpha were used as 'second hit' agents in association with the AO. RESULTS: Western blotting showed a down-regulation in cIAP-1 expression and higher levels of spontaneous apoptosis in both cell types with no alteration in overall cell viability. AO sensitized PC3 cells, to Fas antibody and TNFalpha-mediated apoptosis, but not to apoptosis mediated by paclitaxel or CAPE. CONCLUSIONS: cIAP-1 down-regulation increased spontaneous apoptosis in prostate cancer cells and sensitized PC3 cells to receptor-mediated apoptosis.