Peroxisome proliferator-activated receptor gamma augments tumor necrosis factor family-induced apoptosis in hepatocellular carcinoma.

Abstract	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.
Authors	Hiroshi Okano, Katsuya Shiraki, Hidekazu Inoue, Takenari Yamanaka, Masatoshi Deguchi, Kazushi Sugimoto, Takahisa Sakai, Shigeru Ohmori, Katsuhiko Fujikawa, Kazumoto Murata, Takeshi Nakano
Journal	Anti-cancer drugs (Anticancer Drugs) Vol. 13 Issue 1 Pg. 59-65 (Jan 2002) ISSN: 0959-4973 [Print] England
PMID	11914642 (Publication Type: Journal Article)
Chemical References	Apoptosis Regulatory Proteins Ligands Membrane Glycoproteins Nuclear Proteins Receptors, Cytoplasmic and Nuclear TNF-Related Apoptosis-Inducing Ligand TNFSF10 protein, human Transcription Factors Tumor Necrosis Factor-alpha fas Receptor
Topics	Apoptosis (drug effects) Apoptosis Regulatory Proteins Carcinoma, Hepatocellular (pathology) Cell Division (drug effects) Humans Ligands Liver Neoplasms (pathology) Membrane Glycoproteins (pharmacology) Nuclear Proteins (pharmacology) Receptors, Cytoplasmic and Nuclear TNF-Related Apoptosis-Inducing Ligand Transcription Factors (pharmacology) Tumor Cells, Cultured (drug effects, metabolism, pathology) Tumor Necrosis Factor-alpha (pharmacology) fas Receptor (pharmacology)

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