The apoptosis-inducing effects of polyunsaturated fatty acids (PUFAs) on benign and malignant breast cells in vitro

Three breast cell lines, the malignant MCF-7 and MDA-MB-231 and the immortalized but non-malignant HBL-100 lines, were growth-inhibited in vitro by the polyunsaturated fatty acid, eicosapentaenoic acid at concentrations of 5–20 μM, inhibition being mild for the two malignant lines but strong for the immortalized HBL-100 line. Eicosapentaenoic acid (50 μM) induced moderate lipid peroxidation and extensive loss of viability in the HBL-100 cells, high levels of lipid peroxidation with slight loss of viability in MDA-MB-231 cells and neither peroxidation nor loss of viability in MCF-7 cells. In HBL-100 cells, all 7 polyunsaturated fatty acids tested inhibited growth: cis-parinaric, arachidonic, γ-linolenic and docosahexacnoic acids were the most potent, being effective (IC50) at <1 μM, whereas the mono-unsaturated fatty acids, erucic acid and oleic acid either had no effect, or stimulated growth. Growth-inhibition by polyunsaturated fatty acids was due to induction of cell death with characteristic morphological features of apoptosis. These findings suggest another possible reason why polyunsaturated fatty acids such as a γ-linolenic acid are effective in benign disease including mastalgia; they may inhibit the growth of some proliferating epithelial cells via the induction of apoptosis and this raises the prospect that other polyunsaturated fatty acids may be even more effective.