Inhibition of human chondrosarcoma cell growth via apoptosis by peroxisome proliferator-activated receptor-γ

Abstract

A rare immunohistochemical study using 28 surgical sections of human chondrosarcoma revealed that 67.9% of tumour cells had weak (10-40%) or strong (> 40%) positive immunoreaction for peroxisome proliferator-activated receptor-γ. The expression of peroxisome proliferator-activated receptor-γ mRNA and protein in human chondrosarcoma cell line OUMS-27 was also determined by reverse transcription-polymerase chain reaction and immunocytochemistry, respectively. Furthermore, the effects of peroxisome proliferator-activated receptor-γ ligands on cell proliferation and survival were investigated in OUMS-27 cells. Pioglitazone, a selective ligand for peroxisome proliferator-activated receptor-γ, and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a putative endogenous ligand for peroxisome proliferator-activated receptor-γ, inhibited the proliferation of OUMS-27 cells in a dose-dependent manner. The mechanism of cytotoxic effects of 15d-PGJ2 was via apoptosis as shown by DNA fragmentation using TUNEL stain and DNA ladder formation, and by ultrastructural analysis using transmission electron microscopy. Flow-cytometric analysis using annexin-V-fluorescein and propidium iodide detected the early change of apoptosis, as well as necrosis of OUMS-27 cells at 4 h after co-incubation with 15d-PGJ2. These results suggest that peroxisome proliferator-activated receptor-γ may play a significant role in the pathogenesis of chondrosarcoma, and peroxisome proliferator-activated receptor-γ ligands, especially 15d-PGJ2, may be of therapeutic value in the treatment of human chondrosarcoma. © 2002 Cancer Research UK.