Differential effects of omega-3 and omega-6 Fatty acids on gene expression in breast cancer cells.
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.
Hammamieh
Rasha
R
Division of Pathology, Walter Reed Army Institute of Research, 503 Robert Grant Road, Silver Spring, MD 20910, USA.
Chakraborty
Nabarun
N
Miller
Stacy-Ann
SA
Waddy
Edward
E
Barmada
Mohsen
M
Das
Rina
R
Peel
Sheila A
SA
Day
Agnes A
AA
Jett
Marti
M
D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D025341:Principal Component Analysis
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6