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

Dietary conjugated linoleic acids (CIA) are fatty acid isomers with anticancer activities produced naturally in ruminants or from vegetable oil processing. The anticancer effects of CIA differ upon the cancer origin and the CIA isomers. In this study, we carried out to precise the effects of CIA isomers, c9,t11 and t10,c12 CIA, on mechanisms of cell death induction in colon cancer cells. We first showed that only t10,c12 CIA treatment (25 and 50 mu M) 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 CIA activated ER stress characterized by induction of eIF2 alpha phoshotylation, splicing of Xbp1 mRNA and CHOP expression. Furthermore, we evidenced that inhibition of CHOP expression and JNK signaling decreased t10,c12 CIA-mediated cancer cell death. Finally, we showed that CHOP induction by t10,c12 CIA 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 CIA exerts its cytotoxic effect through ROS generation and a subsequent ER stress-dependent apoptosis in colon cancer cells. (C) 2013 Elsevier B.V. All rights reserved.