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Omega‐3 Polyunsaturated Fatty Acids (n‐3 PUFAs) Decrease Growth and microRNA‐21 Expression of Estrogen Receptor‐Positive (ER+) MCF‐7 Breast Cancer Cells
Author(s) -
LeMayNedjelski Lauren,
Mason Julie,
Taibi Amel,
Comelli Elena,
Thompson Lilian
Publication year - 2015
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.29.1_supplement.752.5
Subject(s) - mcf 7 , polyunsaturated fatty acid , estrogen receptor , microrna , breast cancer , estrogen , cancer research , medicine , cancer , estrogen receptor alpha , endocrinology , chemistry , biology , gene , biochemistry , human breast , fatty acid
microRNA (miR)‐21 plays a role in carcinogenesis and modulates genes regulating cell growth. Consumption of diets rich in the n‐3 PUFA alpha‐linolenic acid (ALA) in animals and humans results in elevations of serum ALA, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Our objective was to determine in vitro the effect of ALA, alone and combined with EPA and DHA (at levels found in serum of animals or humans fed ALA‐rich diets) on growth of MCF‐7 cells and miR‐21 expression changes as an underlying mechanism. Cells were treated with 112μM fatty acids as either ALA alone, or with EPA and DHA at ratios found in serum of animals (AnR; 1:0.4:3.1) or humans (HuR; 1:1:2.5) or control (no PUFA) plus 1nM estrogen, 40μM oleic acid and 40μM linoleic acid. Cell growth was assessed after 24 and 48 hours treatment. miR‐21 expression was analyzed by qPCR after 1 hour treatment. ALA reduced growth by 9% and 28% at 24 and 48 hours, respectively. AnR and HuR reduced cell growth by 82% and 37%, respectively, at 24 hours, and 37% for both at 48 hours. No change in growth was observed at 1 hour. miR‐21 displayed 0.83‐fold, 0.25‐fold and 0.58‐fold changes in expression for ALA, AnR and HuR, respectively, following 1 hour treatment, with AnR miR‐21 significantly downregulated (p=0.0097) compared to control and ALA. A significant relationship was observed between fatty acid effects on miR‐21 at 1 hour and cell growth at 24 hours (R 2 = 0.9980; p= 0.0231). AnR contained the highest level of DHA, suggesting it is most active in reducing cell growth via effects on miR‐21. ALA, when combined with DHA and EPA reduces the growth of ER+ breast cancer cells potentially through early modulation of miR‐21. Funding: NSERC.