Peroxisome proliferator-activated receptor gamma augments tumor necrosis factor family-induced apoptosis in hepatocellular carcinoma.
Proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor, which mainly associates with adipogenesis, but also appears to facilitate cell differentiation or apoptosis in certain malignant cells. This apoptosis induction by PPARgamma is increased by co-stimulation with tumor necrosis factor (TNF)-alpha-related apoptosis-inducing ligand (TRAIL), a member of the TNF family. In this study, we investigated the effect of PPARgamma on Fas-mediated apoptosis in hepatocellular carcinoma (HCC) cell lines. PPARgamma was expressed on all seven HCC cell lines and located in their nuclei. 15-Deoxy-Delta-12,14-prostaglandin J2 (15d- PGJ2), a PPARgamma ligand, inhibited cellular proliferation in HepG2, SK-Hep1 or HLE cells, unlike pioglitazone, another PPARgamma ligand, which did not have a significant influence on proliferation of these cells. However, 15d-PGJ2 facilitated Fas-mediated HCC apoptosis that could not be induced by Fas alone. These results suggest that PPARgamma can augment TNF-family-induced apoptosis.
Okano
Hiroshi
H
First Department of Internal Medicine, Mie University School of Medicine, Tsu 514-8507, Japan.
Shiraki
Katsuya
K
Inoue
Hidekazu
H
Yamanaka
Takenari
T
Deguchi
Masatoshi
M
Sugimoto
Kazushi
K
Sakai
Takahisa
T
Ohmori
Shigeru
S
Fujikawa
Katsuhiko
K
Murata
Kazumoto
K
Nakano
Takeshi
T
D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008113:Liver Neoplasms / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000494:pharmacology; D009687:Nuclear Proteins / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear; D053221:TNF-Related Apoptosis-Inducing Ligand; D014157:Transcription Factors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019014:fas Receptor / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D009687:Nuclear Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor