Antitumor Efficacy of Two Novel Non-Thiazolidinedione Compounds as Peroxisome Proliferator-Activated Receptor-γ Agonists in Human Osteosarcoma Cells in vitro

Background: Due to chemotherapy resistance in osteosarcoma subgroups, the prognosis of these patients is still poor, and the development of new agents is of utmost importance. The aim of our study was to test the antitumor effects of two novel α-aryloxy-α-methylhydrocinnamic acid derivatives as peroxisome proliferator-activated receptor (PPAR) γ agonists, together with rosiglitazone, a well-known thiazolidinedione (TZD) acting on several osteosarcoma cell lines. Methods/Results: The MTT assay revealed that cell viability was inhibited in a dose-dependent manner with IC 50 6.2–15.8 μM for the two novel compounds and rosiglitazone (48.4–83.5 μM). Exposure to DG8 and DH9 at low micromolar concentrations induced a dose-dependent block of DNA synthesis and colony formation. In these antitumor assays, DG8 and DH9 were more effective than rosiglitazone, although the PPARγ agonistic activity of rosiglitazone is much higher. The SiRNA approach to downregulate specifically PPARγ in U-2OS cells did not affect the cytotoxic efficiency of either the two novel compounds or rosiglitazone. Conclusion: These observations suggest that non-TZDs with less PPARγ agonistic activity might show more potent antitumor efficacy independent of PPARγ in human osteosarcoma cells, which supports the possibility that they could be beneficial in the treatment of osteosarcoma patients.