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.
McEleny
Kevin
K
Department of Surgery, Mater Misericordiae University Hospital and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland.
Coffey
Ronan
R
Morrissey
Colm
C
Williamson
Kate
K
Zangemeister-Wittke
Uwe
U
Fitzpatrick
John M
JM
Watson
R William G
RW
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D015536:Down-Regulation; D049668:History, 15th Century; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D014176:Protein Biosynthesis; D011506:Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000970:Antineoplastic Agents; D051034:Inhibitor of Apoptosis Proteins; D016376:Oligonucleotides, Antisense; D011506:Proteins; D014409:Tumor Necrosis Factor-alpha