Epidemiological and experimental data have suggested that long-chain omega-3 polyunsaturated fatty acids (PUFA) of marine origin inhibit the development of breast cancer. We investigated the effects of docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids on the proliferation of MDA-MB-231 human mammary epithelial cells. Both DHA and EPA decreased cell proliferation. To find out whether a specific phase of the cell cycle was affected, we used a flow cytometry approach with cells previously cultured in presence of either PUFA at increasing concentrations. Cells were first synchronised in late G1 and then released into the cycle. The synchronisation was efficient since nearly 90% of the cells moved on together. G1 and S phases were not affected by either fatty acid. In contrast, G2/M duration was increased 1.7-, 4.6- and 7.1-fold at 10, 30 and 50 μM DHA, respectively. Similar findings were observed with EPA. The influence of fatty acids on CDK1 and cyclin B levels was examined using western immunoblotting. The levels of both proteins were reduced by DHA or EPA, indicating that in mammary epithelial cells, these fatty acids act on key regulators of the G2/M transition. Current investigations aim at finding which upstream regulators of CDK1/cyclin B may also be involved.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]