15‐deoxy‐Δ^12,14‐prostaglandin J₂, a ligand for peroxisome proliferators‐activated receptor‐γ, induces apoptosis in human hepatoma cells

Abstract

BACKGROUND/AIMS: 15-deoxy-delta12,14-prostaglandin J2 (15-d-PGJ2) induces apoptosis in several carcinoma cell lines and is a potent activator of peroxisome proliferators-activated receptor-gamma (PPAR-gamma). In the present study, we examined the effect of 15-d-PGJ2 on human hepatoma cells. METHODS: HuH-7 and HepG2 cell lines were used in all the experiments. The mRNA expression of PPAR-gamma was studied by reverse transcriptase-polymerase chain reaction. The cell viability was determined by a modified MTT assay. Two methods were used for the determination of apoptosis in hepatoma cells: the TUNEL assay, and detection of fragmented mono- and oligo-nucleosomes by ELISA. RESULTS: The expression of PPAR-gamma mRNA and protein was detected in HuH-7 and HepG2. Treatment with 15-d-PGJ2 decreased cell viability in a time- and dose-dependent manner. 15-d-PGJ2 induced apoptosis and this effect was time-dependent. Exposure of cells to 15-d-PGJ2 induced caspase-3 and -9 activation. Furthermore, co-treatment with the pan-caspase inhibitor Z-VAD-FMK or the caspase-3 inhibitor Z-DEVD-FMK blocked apoptosis of human hepatoma cells that had been treated with 15-d-PGJ2. CONCLUSIONS: Our study demonstrates that PPAR-gamma is expressed in human hepatoma cell lines and that treatment with 15-d-PGJ2 inhibits the growth of these cells by inducing apoptosis through caspase activation.