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


Masataka Date, MD, PhD,
Department of Pharmacology, Osaka Dental University, 8-1, Kuzuhahanazono-cho, Hirakata, Osaka 573-1121, Japan.
Tel: 81-72-864-3058.
Fax: 81-72-864-3158.
e-mail: date@cc.osaka-dent.ac.jp


Background/Aims: 15-deoxy-Δ12,14-prostaglandin J2 (15-d-PGJ2) induces apoptosis in several carcinoma cell lines and is a potent activator of peroxisome proliferators-activated receptor-γ (PPAR-γ). 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-γ 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-γ 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-γ 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.