title: Trans-10, cis-12 conjugated linoleic acid induced cell death in human colon cancer cells through reactive oxygen species-mediated ER stress.
abstract: Dietary conjugated linoleic acids (CLA) are fatty acid isomers with anticancer activities produced naturally in ruminants or from vegetable oil processing. The anticancer effects of CLA differ upon the cancer origin and the CLA isomers. In this study, we carried out to precise the effects of CLA isomers, c9,t11 and t10,c12 CLA, on mechanisms of cell death induction in colon cancer cells. We first showed that only t10,c12 CLA treatment (25 and 50μM) for 72h triggered apoptosis in colon cancer cells without affecting viability of normal-derived colon epithelial cells. Exposure of colon cancer cells to t10,c12 CLA activated ER stress characterized by induction of eIF2α phoshorylation, splicing of Xbp1 mRNA and CHOP expression. Furthermore, we evidenced that inhibition of CHOP expression and JNK signaling decreased t10,c12 CLA-mediated cancer cell death. Finally, we showed that CHOP induction by t10,c12 CLA was dependent on ROS production and that the anti-oxidant N-acetyl-cysteine reduced CHOP induction-dependent cell death. These results highlight that t10,c12 CLA exerts its cytotoxic effect through ROS generation and a subsequent ER stress-dependent apoptosis in colon cancer cells.
authors: Université de Bourgogne, Centre de Recherche INSERM, UMR866, 6 Boulevard Gabriel, 21000 Dijon, France.
authors: Anne-Sophie
authors: AS
authors: Pierre
authors: Mélaine
authors: M
authors: Minville-Walz
authors: Cécile
authors: C
authors: Fèvre
authors: Aziz
authors: A
authors: Hichami
authors: Joseph
authors: J
authors: Gresti
authors: Laurent
authors: L
authors: Pichon
authors: Sandrine
authors: S
authors: Bellenger
authors: Jérôme
authors: J
authors: Bellenger
authors: François
authors: F
authors: Ghiringhelli
authors: Michel
authors: M
authors: Narce
authors: Mickaël
authors: M
authors: Rialland
mesh_terms: D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D044243:Linoleic Acids, Conjugated; D017382:Reactive Oxygen Species