DHA modifies lipid raft structure and function in MDA-MB-231 breast cancer cells

In vivo and in vitro studies suggest that omega-3 poliunsaturated fatty acids (n-3 PUFA) can be cancer chemopreventive, chemosuppressive and auxiliary agents for cancer therapy (1). N-3 PUFA, like docosaexaenoic acid (DHA), could alter tumor growth by influencing cell replication, interfering with cell cycle components or increasing cell death, either by inducing necrosis or apoptosis. We have observed that DHA induces in MDA-MB-231 cells apoptosis and reduction of cell viability. Moreover, DHA significantly reduces the EGFR level and completely inhibits EGFR activation. However, the mechanism by which n-3 PUFA inhibit breast cancer growth, is not yet well understood. It was suggested that these fatty acids might change cell membrane fluidity and structure, especially of lipid rafts. Our data obtained by HPLC-GC analysis demonstrate that DHA is incorporated and metabolized in MDA-MB-231 membrane. In particular, DHA is incorporated in breast cancer lipid rafts with different specifity for the phospholipid moiety and induces a reduction of cholesterol and sphingomyelin content, indicating a possible change in raft organization. Changes in the lipid raft structure were also analyzed with atomic force microscopy (AFM) and Fourier transform infrared spectroscopy (FTIR). The AFM analysis of breast cancer lipid rafts indicates after DHA incorporation a reduction of microdomains number. Moreover PUFA treated rafts are dimensionally different from control rafts (2). Then, when DHA is incorporated into the cell membrane, it may induce the formation of “declustered rafts” with reorganization of lipids and proteins that may greatly influence signal transduction. 1 Calviello G et al., Nutr Cancer. 2009. 2 Corsetto PA et al., Cell Biochem Biophys. 2012.