Peroxisome proliferator-activated receptor gamma induces pancreatic cancercell apoptosis

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) decreases the growth of certain cancer cells. In the present study, we found that six di fferent human pancreatic cancer cell lines (AsPC-1, BxPC-3, Capan-2, HPAF-I I, MIA PaCa-2, and PANC-1) expressed PPAR-gamma m-RNA and synthesized the p rotein. The endogenous and exogenous PPAR-gamma ligands 15-deoxy-d12,14-pro staglandin J(2) (15-PGJ(2)) and ciglitazone decreased cell number, cell via bility, and increased floating/attached ratio, in a time- and dose-dependen t fashion. 15-PGJ(2) increased intracellular nucleosome concentration after 6 h, but did not increase caspase-3 activity even after 96 h. Combined tre atment with both 15-PGJ(2) and the caspase-3 inhibitor DEVD-CHO had no effe ct on cell viability, but the general caspase inhibitor ZVAD-FMK reduced 15 -PGJ(2)-induced apoptosis. We concluded that the six human pancreatic cance r cells tested all expressed PPAR-gamma receptor, and treatment with PPAR-g amma agonists decreased cell viability and growth in a time- and dose-depen dent manner. These effects were partially mediated by induction of caspase- 3 independent apoptosis. (C) 2001 Academic Press.