15-PGJ2, but not thiazolidinediones, inhibits cell growth, induces apoptosis, and causes downregulation of Stat3 in human oral SCCa cells

Abstract

Activation of peroxisome proliferator-activated receptor gamma (PPARγ) has been linked to induction of differentiation, cell growth inhibition and apoptosis in several types of human cancer. However, the possible effects of PPARγ agonists on human oral squamous cell carcinoma have not yet been reported. In this study, treatment with 15-deoxy-Δ12,14-PGJ2 (15-PGJ2), a natural PPARγ ligand, induced a significant reduction of oral squamous cell carcinoma cell growth, which was mainly attributed to upregulation of apoptosis. Interestingly, rosiglitazone and ciglitazone, two members of the thiazolidinedione family of PPARγ activators, did not exert a growth inhibitory effect. Given the critical role that the oncogene signal transducer and activator of transcription 3 (Stat3) plays in head and neck carcinogenesis, its potential regulation by PPARγ ligands was also examined. Treatment of oral squamous cell carcinoma cells with 15-PGJ2 induced an initial reduction and eventual elimination of both phosphorylated and unphosphorylated Stat3 protein levels. In contrast, other PPARγ did not induce similar effects. Our results provide the first evidence of significant antineoplastic effects of 15-PGJ2 on human oral squamous cell carcinoma cells, which may be related to downmodulation of Stat3 and are at least partly mediated through PPARγ-independent events