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15‐deoxy‐Δ 12,14 ‐prostaglandin J 2 , a ligand for peroxisome proliferators‐activated receptor‐γ, induces apoptosis in human hepatoma cells
Author(s) -
Date Masataka,
Fukuchi Kazuhide,
Morita Shosuke,
Takahashi Hiroshi,
Ohura Kiyoshi
Publication year - 2003
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2003.00877.x
Subject(s) - apoptosis , microbiology and biotechnology , viability assay , cell culture , receptor , peroxisome proliferator activated receptor , mtt assay , biology , chemistry , biochemistry , genetics
Background/Aims: 15‐deoxy‐Δ 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‐γ (PPAR‐γ). In the present study, we examined the effect of 15‐d‐PGJ 2 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‐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‐γ 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.