Inhibition of human lung cancer cell growth by the peroxisome proliferator-activated receptor-gamma agonists through induction of apoptosis

Peroxisome proliferator-activated receptors (PPARs), members of the nuclear hormone receptors superfamily, have an important regulatory role in adipog enesis and inflammation. PPAR-gamma Ligands induce terminal differentiation and growth inhibition of human breast cancer cells and prostatic cancer ce lls. In this study, we demonstrated that PPAR-gamma, but not PPAR-alpha, wa s expressed in human lung cancer cell lines by reverse transcription-polyme rase chain reaction (RT-PCR) and Western blot analysis. We also found that the synthetic PPAR-gamma agonist thiazolidinedione compounds (troglitazone) and the endogenous PPAR-gamma hgand, 15-deoxy-Delta(12,14)-prostaglandin J (2) (15d-PGJ(2)), inhibited the growth of human lung cancer cells through t he induction of apoptosis. However, PPAR-alpha agonist (bezafibrate) and ot her prostanoids (PGE(2), PGF(2 alpha)) did not induce apoptosis. These find ings suggest that PPAR-gamma may play an important role in the pathogenesis of lung cancer and that PPAR-gamma agonist may be useful therapeutic agent s in the treatment of human lung cancer. (C) 2000 Academic Press.