Caffeic acid phenethyl ester-induced PC-3 cell apoptosis is caspase-dependent and mediated through the loss of inhibitors of apoptosis proteins.
OBJECTIVE
To investigate the effects of a novel agent, caffeic acid phethyl ester (CAPE) on nuclear factor (NF)-kappaB activation and apoptosis in the androgen-independent PC3 prostate cancer cell line.


METHODS
PC-3 cells were assessed for NF-kappaB activation induced by paclitaxel and tumour necrosis factor-alpha (TNF-alpha), using a p65 enzyme-linked immunosorbent assay, with or without CAPE treatment. The corresponding apoptosis was assessed with propidium iodide DNA staining using flow cytometry. The pan-caspase inhibitor Z-VAD-FMK was used to investigate the mechanism of apoptosis. Alterations in the expression of inhibitor of apoptosis proteins (IAP), cIAP-1, cIAP-2 and XIAP, were detected using western blot analysis.


RESULTS
CAPE prevented paclitaxel and TNFalpha-mediated NF-kappaB activation. Its ability to induce apoptosis in a dose-dependent manner was associated with the loss of cIAP-1, cIAP-2 and XIAP expression. Pretreatment with Z-VAD-FMK prevented CAPE-induced apoptosis and the loss of the IAPs.


CONCLUSIONS
CAPE is an effective inhibitor of NF-kappaB activation in PC-3 cells, but the mechanism of apoptosis, and the corresponding loss of IAP expression, is caspase-dependent.
Department of Surgery, Mater Misericordiae University Hospital, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Ireland.
Kevin
K
McEleny
Ronan
R
Coffey
Colm
C
Morrissey
John M
JM
Fitzpatrick
R William G
RW
Watson
D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002109:Caffeic Acids / Q000494:pharmacology*; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002109:Caffeic Acids; D061945:Caspase Inhibitors; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol; D017239:Paclitaxel