Exploration of mechanisms of α-linolenic acid in reducing the growth of oestrogen receptor positive breast cancer cells (MCF-7)

• α-Linolenic acid (ALA) reduces oestrogen receptor-positive breast cancer cell growth.
• ALA modulates oestrogen receptor-related gene and protein expression.
• Oestrogen receptor modulation by ALA is independent of its metabolites.

The n-3 fatty acid α-linolenic acid (ALA) inhibits oestrogen receptor (ER) positive MCF-7 cell growth in vitro and in vivo. Our objective was to explore potential mechanisms. MCF-7 cells were treated with 100 µM ALA and 1 nM oestradiol (E2) then analysed for fatty acid profile, mRNA and protein biomarkers compared to an E2-containing control. The independent and combined effects of ALA, ER activator (E2) and antagonist (ICI-182,780, fulvestrant) on cell growth were determined. ALA was incorporated into cells but not further metabolized. ALA modulated the mRNA expression of targets regulated by or that regulate the ER including caveolin-1, survivin and progesterone receptor (PGR). Lower cyclin-D1, PGR, caveolin-1 and higher ERα protein expression were seen in ALA-treated cells. Co-incubation with ICI-182,780 negated the growth-reducing effect of ALA. In conclusion, ALA may reduce MCF-7 growth by modulating ER-related signalling, thus suggesting a plausible mechanism for ALA independent of its metabolites.