Trans-10, cis-12 conjugated linoleic acid induced cell death in human colon cancer cells through reactive oxygen species-mediated ER stress

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• 作者：Anne-Sophie Pierre¹ ; Mé ; laine Minville-Walz¹ ; Cé ; cile Fè ; vre ; Aziz Hichami ; Joseph Gresti ; Laurent Pichon ; Sandrine Bellenger ; Jé ; rô ; me Bellenger ; Franç ; ois Ghiringhelli ; Michel Narce² ; Mickaë ; l Rialland ; ² ; ^{mickael.rialland@u-bourgogne.fr}
• 关键词：CHOP ; C/EBP homologous protein ; CLA ; Conjugated linoleic acids ; ER ; Endoplasmic reticulum ; IRE1 ; Inositol requiring enzyme 1 ; JNK ; c-Jun NH(2)-terminal kinase ; PERK ; RNA-dependent protein kinase (PKR)-like ER kinase ; ROS ; Reactive oxygen species ; UPR ; Unf
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：2013
• 出版时间：April, 2013
• 年：2013
• 卷：1831
• 期：4
• 页码：759-768
• 全文大小：1562 K

文摘

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 50 ¦ÌM) for 72 h 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 eIF2¦Á 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.