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Recently, we have demonstrated that omega-6 fatty acid linoleic acid (LA) in presence of estradiol (E2) enhances proliferation and anchorage independent growth with down regulation of BRCA1 mRNA expression in MCF-7 cell line. Since omega-3 fatty acid (docosahexanoic acid, DHA) is known to block the promoting effect of omega-6 polyunsaturated fatty acid (LA), we wanted to see whether addition of DHA can inhibit the growth of MCF-7 cells which are exposed to LA + E2 and any alteration of BRCA1 mRNA expression could be seen in DHA treated culture. Experiments on MCF-7 cells with DHA revealed both decrease in proliferation and anchorage independency as compared to controls; while no change of BRCA1 mRNA expression was observed. Further, when DHA was administered to cells along with LA + E2, no change in BRCA1 expression was observed, however, a marked decrease in proliferation and soft agar colony formation was evident, indicating inhibition of MCF-7 cells following DHA treatment. Flow cytometric analysis showed that DHA treated cells either alone or in combination with LA + E2 induced marked G1/S and G2/M arrest of the cells, suggesting the inhibitory effect of DHA at this phase of cell cycle. However, neither typical DNA ladder nor fragmented nuclei or apoptotic bodies were observed, ruling out presence of apoptosis following DHA treatment.

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Using clonal cell cultures, a significant increase in chromosomal aberrations (aneuplolidy, dicentrics and chromatid breaks) were observed in MCF-7 cells compared with HeLa. BRCA1 expression was lower in MCF-7 cells than in HeLa cells. Since BRCA1 is known to play a role in the maintenance of chromosomal integrity, the increase in chromosomal aberrations in MCF-7 clones suggests that downregulation of BRCA1 expression could be one of the possible mechanisms for increased chromosomal instability in this cell line.