TY - JOUR
T1 - Inhibition of human chondrosarcoma cell growth via apoptosis by peroxisome proliferator-activated receptor-γ
AU - Nishida, K.
AU - Furumatsu, T.
AU - Takada, I.
AU - Kawai, A.
AU - Yoshida, A.
AU - Kunisada, T.
AU - Inoue, H.
PY - 2002/4/22
Y1 - 2002/4/22
N2 - 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.
AB - 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.
KW - 15d-PGJ
KW - Apoptosis
KW - Chondrosarcoma
KW - PPARγ
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UR - http://www.scopus.com/inward/citedby.url?scp=0037156938&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6600241
DO - 10.1038/sj.bjc.6600241
M3 - Article
C2 - 11953889
AN - SCOPUS:0037156938
SN - 0007-0920
VL - 86
SP - 1303
EP - 1309
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 8
ER -
