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Troglitazione affects survival of human osteosarcoma cells
Enrico Lucarelli1, Luca Sangiorgi, Veronica Maini
1Laboratory of Oncology Research, Rizzoli Orthopedic Institute, Bologna, Italy. enrico.lucarelli@ior.it
Abstract:
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.
Insights
Troglitazone (TRO), a PPAR gamma agonist, did not induce apoptosis in osteosarcoma cells. Instead, TRO decreased natural apoptosis, promoting cell survival via the Akt pathway.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Peroxisome proliferator-activated receptor gamma (PPARγ) activation typically induces apoptosis in cancer cells.
- Osteosarcoma (OS) is a primary bone cancer with limited treatment options.
Purpose of the Study:
- To investigate the effect of troglitazone (TRO), a PPARγ agonist, on apoptosis in human osteosarcoma cell lines.
- To explore the underlying mechanisms of TRO's action in OS cells.
Main Methods:
- Treatment of human osteosarcoma cell lines (G292, MG63, SAOS, U2OS) with TRO.
- MTT proliferation assays to assess cell number.
- Assessment of apoptosis induction and prevention.
- Analysis of Akt pathway activation.
Main Results:
- TRO did not induce apoptosis in any of the tested OS cell lines.
- TRO significantly increased OS cell number by reducing spontaneous apoptosis, not by increasing proliferation.
- TRO demonstrated a protective effect against staurosporine-induced apoptosis.
- TRO-mediated cell survival correlated with the activation of the Akt signaling pathway.
Conclusions:
- Troglitazone exhibits a novel cell survival-promoting function in human osteosarcoma cells, contrary to its known apoptotic effects in other cell types.
- The Akt survival pathway is implicated as a key mediator of troglitazone's protective effects in osteosarcoma.
- These findings suggest a potential therapeutic strategy targeting the Akt pathway in osteosarcoma treatment.