Premium
Omega‐3 polyunsaturated fatty acids alter raft lipid composition and decrease epidermal growth factor receptor levels in lipid rafts of human breast cancer cells
Author(s) -
Field Catherine J.,
Schley Patricia D.,
Brindley David N.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a165-c
Subject(s) - lipid raft , docosahexaenoic acid , ceramide , eicosapentaenoic acid , sphingomyelin , chemistry , linoleic acid , epidermal growth factor , endocrinology , polyunsaturated fatty acid , biochemistry , medicine , apoptosis , fatty acid , cholesterol , biology , receptor
To determine the mechanism by which the n‐3 fatty acids (FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) decrease proliferation and induce apoptosis in MDA‐MB‐231 human breast cancer cells, we examined the effects of EPA and DHA on the lipid composition of lipid rafts as well as epidermal growth factor receptor (EGFR) raft localization and phosphorylation. N‐3 FA (a combination of EPA and DHA) inhibited the growth of MDA‐MB‐231 cells by 48–62% (p<0.05) in the presence and absence, respectively, of linoleic acid. EPA and DHA were incorporated significantly into lipid rafts isolated from MDA‐MB‐231 cells after treatment with n‐3 FA (p<0.05). EPA and DHA treatment significantly decreased (p<0.05) lipid raft sphingomyelin, cholesterol, and diacylglycerol content and, in the absence of linoleic acid, EPA and DHA increased raft ceramide levels. Furthermore, there was a marked decrease in EGFR levels in lipid rafts, accompanied by increases in the phosphorylation of both EGFR and p38 MAPK, in EPA/DHA‐treated cells. As sustained activation of the EGFR and p38 MAPK has been associated with apoptosis in human breast cancer cells, our results indicate that omega‐3 FA modify the lipid composition of membrane rafts and alter EGFR signaling in a way that decreases the growth of breast tumors.