15-deoxy-Δ12,14-prostaglandin J2, a ligand for peroxisome proliferators-activated receptor-γ, induces apoptosis in human hepatoma cells

Background/Aims: 15-deoxy-Delta(12,14)-prostaglandin J(2) (15-d-PGJ(2)) 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-PGJ(2) on human hepatoma cells. Methods: <LF>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-PGJ(2) decreased cell viability in a time- and dose-dependent manner. 15-d-PGJ(2) induced apoptosis and this effect was time-dependent. Exposure of cells to 15-d-PGJ(2) 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-PGJ(2). Conclusions: Our study demonstrates that PPAR-gamma is expressed in human hepatoma cell lines and that treatment with 15-d-PGJ(2) inhibits the growth of these cells by inducing apoptosis through caspase activation.