Troglitazione affects survival of human osteosarcoma cells.
Activation of PPAR gamma, a transcription factor member of the family of peroxisome proliferator-activated receptors, induces apoptosis in several normal and tumor cell lines. In our study, we investigated whether treatment with troglitazone (TRO), a known PPAR gamma agonist, induced apoptosis in the human osteosarcoma (OS) cell lines G292, MG63, SAOS and U2OS that express PPAR gamma. In our experiments, TRO never induced apoptosis of OS cells; on the contrary, TRO increased cell number, based on MTT proliferation assay. Remarkably, the TRO-induced cell number increase depended on a decrease of apoptosis that naturally occurred in the culture and was not due to an increased cell proliferation rate. TRO also prevented staurosporin-induced apoptosis. The TRO-mediated survival effect correlated with the activation of Akt, a well-known mediator of survival stimuli. Our work describes a new function for TRO and indicates that the Akt survival pathway may be a mediator of TRO-induced increase of survival.
Lucarelli
Enrico
E
Laboratory of Oncology Research, Rizzoli Orthopedic Institute, Bologna, Italy. enrico.lucarelli@ior.it
Sangiorgi
Luca
L
Maini
Veronica
V
Lattanzi
Giovanna
G
Marmiroli
Sandra
S
Reggiani
Matteo
M
Mordenti
Marina
M
Alessandra Gobbi
Giuliana
G
Scrimieri
Francesca
F
Zambon Bertoja
Annarosa
A
Picci
Piero
P
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D002452:Cell Count; D002455:Cell Division; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology*; D006801:Humans; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists / Q000378:metabolism; D000077288:Troglitazone; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D000970:Antineoplastic Agents; D002839:Chromans; D011518:Proto-Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D000077288:Troglitazone