2007, “Apoptotic action of peroxisome proliferator-activated receptor-gamma activation in human non small-cell lung cancer is mediated via proline oxidase-induced reactive oxygen speciesd formation

Peroxisome proliferator-activated receptor (PPAR)- ligands have been shown to inhibit human lung cancers by inducing apoptosis and differentiation. In the present study, we eluci-dated the apoptotic mechanism of PPAR activation in human lung cancers by using a novel PPAR agonist, 1-(trans-methyl-imino-N-oxy)-6-(2-morpholinoethoxy)-3-phenyl-(1H-indene-2-carboxylic acid ethyl ester (KR-62980), and rosiglitazone. PPAR activation selectively inhibited cell viability of non– small-cell lung cancer with little effect on small-cell lung cancer and normal lung cells. The cell death induced by PPAR acti-vation presented apoptotic features of oligonucleosomal DNA fragmentation in A549 human non–small-cell lung cancer cell line. Reactive oxygen species (ROS) production was accompa-nied by increased expression of proline oxidase (POX), a redo