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

Anti-cancer Drugs
Hiroshi OkanoTakeshi Nakano

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.

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Citations

May 30, 2008·PPAR Research·Ivan Borbath, Yves Horsmans
Aug 30, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Syed Z ImamWei-Dong Le
Jul 20, 2014·Molecular Biology Reports·Sundas FayyazAmmad Ahmad Farooqi

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