Abstract

The dietary fat hypothesis postulates that dietary or exogenously derived fatty acids play an important role in the carcinogenesis, evolution and/or progression of breast cancer. In order to reveal possible underlying mechanisms of this hypothesis, we studied the influence of ω- 3 polyunsaturated fatty acids (PUFAs) -α-linolenic (ALA), eicosapentaenoic (EPA) and docosahexaenoic (DHA)-, ω-6 PUFAs-linoleic (LA), γ-linolenic (GLA) and arachidonic (ARA)- and monounsaturated ω- 9 oleic acid (OA) on the proliferation, adhesion and metastatic potential of human breast cancer cells in culture. GLA and the ω-3 PUFAs, ALA and DHA, inhibited significantly the cell growth of MCF-7 and MDA-MB-231 breast cancer cell lines, while EPA has less marked inhibitory effects. ω-6 PUFAs, LA and ARA, or ω- 9 OA had either no effect or caused a slight increase of proliferation. The attachment of breast cancer cells to the extracellular matrix components (type IV collagen, fibronectin and Matrigel) was significantly inhibited by ω-6 GLA and ω-3 PUFAs ALA, DHA and EPA. At concentrations which had no effect on cell growth over the duration of experiments the ω-6 PUFAs, LA and GLA, and the ω-3 PUFAs, ALA, DHA and EPA, had the ability to inhibit both cellular migration and invasion into type IV collagen and Matrigel. In summary, our findings indicate important differences in the ability of ω-3, ω-6 and ω-9 fatty acids to modulate prolif eration, attachment to extracellular matrix components, mo-tility and invasiveness of human breast carcinoma cells in vitro, with the GLA and all ω-3 PUFAs being the most effective inhibitors. Our data are consistent with the view that the type rather than the amount of dietary fatty acids is be more important in breast cancer development and progression.

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