Submitted on August 29, 2007
Revised on June 19, 2008
Accepted on June 19, 2008
DHA induces ER stress and growth arrest in human colon cancer cells - associations with cholesterol and calcium homeostasis
Caroline Hild Jakobsen, Gro Leite Størvold, Hilde Bremseth, Turid Follestad, Kristin Sand, Merete Mack, Karina Standahl Olsen, Anne Gøril Lundemo, Jens Gustav Iversen, Hans Einar Krokan, and Svanhild Margrethe Arentz Schønberg
Laboratory Medicine, Children's and Women's Health, Medical Faculty, Norwegian University of Science and Technology, Trondheim N-7006
Corresponding Author: svanhild.schonberg{at}ntnu.no
Polyunsaturated fatty acids (PUFAs) are normal constituents of the diet, but have properties different from other fatty acids, for example through generation of signaling molecules. N-3 PUFAs reduce cancer cell growth, but no unified mechanism has been identified. We show that docosahexaenoic acid (DHA; 22:6 n-3) causes extensive changes in gene expression patterns at mRNA level in the colon cancer cell line SW620. Early changes include unfolded protein response (UPR) and increased levels of phosphorylated eIF2
as verified at protein level. The latter is considered a hallmark of endoplasmic reticulum (ER) stress, and is abundantly present already after 3 h. It may coordinate many of the downstream changes observed, including signaling pathways for cell cycle arrest/apoptosis, calcium homeostasis, cholesterol metabolism, ubiquitination and proteasomal degradation. Also, eicosapentaenoic acid (EPA), but not oleic acid (OA), induced key mediators of ER stress and UPR at protein level. Accumulation of esterified cholesterol was not compensated for by increased total levels of cholesterol and mRNAs for cholesterol biosynthesis as well as de novo synthesis of cholesterol were reduced. These results suggest that cytotoxic effects of DHA are associated with signaling pathways involving both lipid metabolism and ER stress.
F1000 Biology *Recommended* - FREE!
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?