Effects of PPAR-γ agonists on oral cancer cell lines: Potential horizons for chemopreventives and adjunctive therapies

Background: Peroxisome proliferator-activated receptor-gamma (PPAR-γ) activators have anti-cancer effects. Our objective was to determine the effect of PPAR-γ ligands 15-deoxy-D^12,14-Prostaglandin J₂ (15-PGJ₂) and ciglitazone on proliferation, apoptosis, and NF-κB in human oral squamous cell carcinoma cell lines. Methods: NA and CA9-22 cells were treated in vitro with 15-PGJ₂ and ciglitazone. Proliferation was measured by MTT colorimetric assay and cell cycle analysis performed via flow cytometry, apoptosis by caspase-3 colorimetric assay and poly-(ADP-ribose) polymerase cleavage on Western blot, and NF-κB activation by luciferase assays. Results: MTT assays demonstrated dose-dependent decreases after 15-PGJ₂ treatment in both cell lines, and S-phase cell cycle arrest was also demonstrated. NF-κB luciferase reporter gene activity decreased seven- and eightfold in NA and CA9-22 cells, respectively. Caspase-3 activity increased two- and eightfold in NA and CA9-22 cells, respectively. Conclusions: Our results suggest these agents, in addition to activating PPAR-γ, can downregulate NF-κB and potentiate apoptosis in oral cancer cells.