Premium
Caffeic acid phenethyl ester‐induced PC‐3 cell apoptosis is caspase‐dependent and mediated through the loss of inhibitors of apoptosis proteins
Author(s) -
McEleny Kevin,
Coffey Ronan,
Morrissey Colm,
Fitzpatrick John M.,
Watson R. William G.
Publication year - 2004
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/j.1464-410x.2004.04936.x
Subject(s) - caffeic acid phenethyl ester , xiap , apoptosis , inhibitor of apoptosis , propidium iodide , chemistry , inhibitor of apoptosis domain , caspase 8 , microbiology and biotechnology , caspase , tumor necrosis factor alpha , caspase 3 , programmed cell death , cancer research , biology , biochemistry , immunology , caffeic acid , antioxidant
OBJECTIVE To investigate the effects of a novel agent, caffeic acid phethyl ester (CAPE) on nuclear factor (NF)‐κB activation and apoptosis in the androgen‐independent PC3 prostate cancer cell line. MATERIALS AND METHODS PC‐3 cells were assessed for NF‐κB activation induced by paclitaxel and tumour necrosis factor‐α (TNF‐α), 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 TNFα‐mediated NF‐κB 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‐κB activation in PC‐3 cells, but the mechanism of apoptosis, and the corresponding loss of IAP expression, is caspase‐dependent.