Differential Effects of Omega-3 and Omega-6 fatty Acids on Gene Expression in Breast Cancer Cells

Abstract

Essential fatty acids have long been identified as possible oncogenic factors. Existing reports suggest omega-6 (omega-6) essential fatty acids (EFA) as pro-oncogenic and omega-3 (omega-3) EFA as anti-oncogenic factors. The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), inhibit the growth of human breast cancer cells while the omega-6 fatty acids induces growth of these cells in animal models and cell lines. In order to explore likely mechanisms for the modulation of breast cancer cell growth by omega-3 and omega-6 fatty acids, we examined the effects of arachidonic acid (AA), linoleic acid (LA), EPA and DHA on human breast cancer cell lines using cDNA microarrays and quantitative polymerase chain reaction. MDA-MB-231, MDA-MB-435s, MCF-7 and HCC2218 cell lines were treated with the selected fatty acids for 6 and 24 h. Microarray analysis of gene expression profiles in the breast cancer cells treated with both classes of fatty acids discerned essential differences among the two classes at the earlier time point. The differential effects of omega-3 and omega-6 fatty acids on the breast cancer cells were lessened at the late time point. Data mining and statistical analyses identified genes that were differentially expressed between breast cancer cells treated with omega-3 and omega-6 fatty acids. Ontological investigations have associated those genes to a broad spectrum of biological functions, including cellular nutrition, cell division, cell proliferation, metastasis and transcription factors etc., and thus presented an important pool of biomarkers for the differential effect of omega-3 and omega-6EFAs.

Reactive Oxygen Species Abrogate the Anticarcinogenic Effect of Eicosapentaenoic Acid in Atm-Deficient Mice

“…Our results confirmed the antiproliferative effect of EPA as shown in Atm-deficient mouse thymoma cells (AT-4), whereas the effect of the n-6 PUFA AA was marginal (24). We showed that the antiproliferative action of EPA is ATM independent, comparing the effect of EPA on cell viability of Atm-deficient and wild-type cells.…”

Regulation of inflammatory and lipid metabolism genes by eicosapentaenoic acid-rich oil

“…There have been several comprehensive analyses of transcription responses to 3-PUFAs, including in PBMC following fi sh oil supplementation ( 19 ), in adipose tissue following a high-PUFA diet in humans ( 20 ) and mice ( 21 ), in breast cancer cell lines treated with EPA and DHA ( 22 ), and in colon cancer cells treated with DHA ( 23 ), to name a few. In the present studies, the model system was biased to examine the anti-infl ammatory responses of 3-PUFAs by using a human monocytic cell line challenged with LPS.…”

Colorectal cancer cell growth inhibition by linoleic acid is related to fatty acid composition changes

“…However, in most studies, even in some in vivo experiments, the researchers compared the functions of n-3 PUFAs and n-6 PUFAs in fatty acid metabolism by treating the cells or animals with the same concentration of fatty acids, without consideration of the normal cell or the fatty acid ratio of the body (Berquin et al, 2007;Hammamieh et al, 2007). Actually, n-6 PUFAs accounted for 35% of the fatty acid composition, and n-3 PUFAs accounted for only 5% in serum (Conquer et al, 1999), suggesting that the n-6 PUFAs were almost seven times as prevalent as n-3 PUFAs.…”