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 immorta lized but non-malignant HBL-100 lines, were growth-inhibited in vitro by th e polyunsaturated fatty acid, eicosapentaenoic acid at concentrations of 5- 20 mu M, inhibition being mild for the two malignant lines but strong for t he immortalized HBL-100 line. Eicosapentaenoic acid (50 mu M) induced moder ate 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. I n HBL-100 cells, all 7 polyunsaturated fatty acids tested inhibited growth: cis-parinaric, arachidonic, gamma-linolenic and docosahexaenoic acids were the most potent, being effective (IC50) at <1 mu M, whereas the mono-unsat urated fatty acids, erucic acid and oleic acid either had no effect, or sti mulated growth. Growth-inhibition by polyunsaturated fatty acids was due to induction of cell death with characteristic morphological features of apop tosis. These findings suggest another possible reason why polyunsaturated fatty ac ids such as gamma-linolenic acid are effective in benign disease including mastalgia; they may inhibit the growth of some proliferating epithelial cel ls via the induction of apoptosis and this raises the prospect that other p olyunsaturated fatty acids may be even more effective.