Effects of n-3 PUFAs on breast cancer cells through their incorporation in plasma membrane

Abstract

BackgroundPUFAs are important molecules for membrane order and function; they can modify inflammation-inducible cytokines production, eicosanoid production, plasma triacylglycerol synthesis and gene expression. Recent studies suggest that n-3 PUFAs can be cancer chemopreventive, chemosuppressive and auxiliary agents for cancer therapy. N-3 PUFAs could alter cancer growth influencing cell replication, cell cycle, and cell death. The question that remains to be answered is how n-3 PUFAs can affect so many physiological processes. We hypothesize that n-3 PUFAs alter membrane stability, modifying cellular signalling in breast cancer cells.MethodsTwo lines of human breast cancer cells characterized by different expression of ER and EGFR receptors were treated with AA, EPA or DHA. We have used the MTT viability test and expression of apoptotic markers to evaluate the effect of PUFAs on cancer growth. Phospholipids were analysed by HPLC/GC, to assess n-3 incorporation into the cell membrane.ResultsWe have observed that EPA and DHA induce cell apoptosis, a reduction of cell viability and the expression of Bcl2 and procaspase-8. Moreover, DHA slightly reduces the concentration of EGFR but EPA has no effect. Both EPA and DHA reduce the activation of EGFR.N-3 fatty acids are partially metabolized in both cell lines; AA is integrated without being further metabolized. We have analysed the fatty acid pattern in membrane phospholipids where they are incorporated with different degrees of specificity. N-3 PUFAs influence the n-6 content and vice versa.ConclusionsOur results indicate that n-3 PUFA feeding might induce modifications of breast cancer membrane structure that increases the degree of fatty acid unsaturation. This paper underlines the importance of nutritional factors on health maintenance and on disease prevention.

Chemical–Physical Changes in Cell Membrane Microdomains of Breast Cancer Cells After Omega-3 PUFA Incorporation

“…after 72 hrs of treatment [20] and were able to incorporate fatty acids, to metabolize them and to insert them into cell membrane lipid rafts, as indicated by present data. The existence of elongases and desaturases able to metabolize PUFA is reported in many tumor cells [37].…”

“…Interestingly previous results from our lab [20] demonstrated that MCF-7 and MDA-MB231 cell membrane are rich of oleic acid with a very low saturation index around 0.5.…”

“…The chromatographic separation is carried out as previously described [20]. Evaporative Light Scattering Detector (ELSD) is used to detect and quantify separated PL species, in comparison with calibration standard curves.…”

Two ABCB4 point mutations of strategic NBD-motifs do not prevent protein targeting to the plasma membrane but promote MDR3 dysfunction

“…20 An ELSD was used to detect and separate the phospholipid species. Cells were then collected using trypsin-EDTA, centrifuged and pellets were analyzed to evaluate protein content.…”

Lipid Metabolism, Metabolic Syndrome, and Cancer

“…Paola et al [88] used MTT viability test and expression of apoptotic markers to evaluate the effect of PUFAs on cancer growth, and their results indicated that EPA and DHA might induce modifications of tumor cell membrane structure leading to an obviously decreased induction rate of breast cancer. Menéndez et al [89] also reported that omega-3 PUFAs ALA suppresses the overexpression of HER2, which plays an important role in aetiology, progression and chemosensitivity of various types of human cancers, suggesting that ALA is a potential anticancer agent.…”