title: The PPARgamma ligand, 15-Deoxy-Delta12,14-PGJ2, regulates apoptosis-related protein expression in cholangio cell carcinoma cells.
abstract: PPARgamma is known to induce apoptosis in malignant tumor cells, but the mechanism of this induction is not well understood. We investigated induction of apoptosis with 15-Deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), a PPARgamma ligand, in cholangio cell carcinoma (CCC) cells (RBE, ETK-1 or HuCCT-1). Apoptosis was induced in RBE and ETK-1 cells with 15d-PGJ2, but not in HuCCT-1 cells, although PPARgamma was expressed in all CCC cells. Apoptosis-related proteins were also expressed, including FLIP, bclx, Apaf-1 and XIAP, but expression levels differed among the three cell lines. RBE cells treated with 15d-PGJ2 showed caspase activation, and it appeared that PPARgamma-induced apoptosis was dependent on caspase activation. However, neither ETK-1 nor HuCCT-1 cells showed significant activation of caspase-8 or -3 with 15d-PGJ2 treatment, raising the possibility of a caspase-independent apoptosis induction pathway. XIAP was down-regulated by 15d-PGJ2 in all three CCC cell lines. Therefore, 15d-PGJ2 induces apoptosis in CCC cells via caspase-dependent or independent pathways. 15d-PGJ2 may also induce down-regulation of XIAP and may promote caspase cascade activation through TNF-family receptor signaling pathways.
authors: First Department of Internal Medicine, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
authors: Hiroshi
authors: H
authors: Okano
authors: Katsuya
authors: K
authors: Shiraki
authors: Hidekazu
authors: H
authors: Inoue
authors: Tomoyuki
authors: T
authors: Kawakita
authors: Masatoshi
authors: M
authors: Deguchi
authors: Kazushi
authors: K
authors: Sugimoto
authors: Takahisa
authors: T
authors: Sakai
authors: Kazumoto
authors: K
authors: Murata
authors: Takeshi
authors: T
authors: Nakano
authors: Munechika
authors: M
authors: Enjoji
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D018281:Cholangiocarcinoma / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014176:Protein Biosynthesis
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D007155:Immunologic Factors; D015230:Prostaglandin D2