Chemical-physical changes in breast cancer lipid rafts after omega-3 PUFA incorporation

Recent studies suggest that ω-3 PUFA can be cancer chemopreventive, chemosuppressive and auxiliary agents for cancer therapy. ω-3 PUFA could alter cancer growth influencing cell replication, cell cycle, and cell death. The mechanisms of PUFA action are still unclear. The aim of this study is to demonstrate that ω-3 PUFA reduce breast adenocarcinoma growth through their incorporation in cell membrane, especially in lipid rafts. We have observed with viability tests, cell morphology analyses and apoptotic markers levels, that EPA and DHA induce apoptosis. We have demonstrated that AA, EPA and DHA are incorporated in breast cancer membrane and isolated lipid rafts with different specificity for the phospholipids moiety. Only the treatment with DHA induces a reduction of cholesterol content in lipid rafts, indicating a possible change in rafts organization. Physical changes in the breast cancer lipid rafts were also assessed with atomic force microscopy (AFM) after ω-3 treatment. The reduction of saturation degree and cholesterol content might induce membrane structural instability causing proteins (i.e. EGFR) displacement. In fact we have observed that in MDA-MB-231 cells, DHA reduces the EGFR content, but not EPA. Both ω-3 PUFA reduce the activation of EGFR. In conclusion, ω-3 PUFA alter lipid raft stability and might modify cellular signalling in breast cancer cells.