title: Peroxisome proliferator-activated receptor gamma induces pancreatic cancer cell apoptosis.
abstract: Peroxisome proliferator-activated receptor gamma (PPAR-gamma) decreases the growth of certain cancer cells. In the present study, we found that six different human pancreatic cancer cell lines (AsPC-1, BxPC-3, Capan-2, HPAF-II, MIA PaCa-2, and PANC-1) expressed PPAR-gamma m-RNA and synthesized the protein. The endogenous and exogenous PPAR-gamma ligands 15-deoxy-d12,14-prostaglandin J(2) (15-PGJ(2)) and ciglitazone decreased cell number, cell viability, and increased floating/attached ratio, in a time- and dose-dependent fashion. 15-PGJ(2) increased intracellular nucleosome concentration after 6 h, but did not increase caspase-3 activity even after 96 h. Combined treatment with both 15-PGJ(2) and the caspase-3 inhibitor DEVD-CHO had no effect on cell viability, but the general caspase inhibitor ZVAD-FMK reduced 15-PGJ(2)-induced apoptosis. We concluded that the six human pancreatic cancer cells tested all expressed PPAR-gamma receptor, and treatment with PPAR-gamma agonists decreased cell viability and growth in a time- and dose-dependent manner. These effects were partially mediated by induction of caspase-3 independent apoptosis.
authors.affiliation: Gastrointestinal Surgery Section, Division of General Surgery, UCLA School of Medicine, 72-215 CHS, 10833 LeConte Avenue, Los Angeles, California 90095-6904, USA.
authors.forename: G
authors.initials: G
authors.lastname: Eibl
authors.forename: M N
authors.initials: MN
authors.lastname: Wente
authors.forename: H A
authors.initials: HA
authors.lastname: Reber
authors.forename: O J
authors.initials: OJ
authors.lastname: Hines
mesh_terms: D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D010190:Pancreatic Neoplasms / Q000473:pathology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases