Journal Article

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

Zava, Stefania, Rizzo, Angela M, Jovenitti, Ilaria E, Cremona, Andrea, Corsetto, Paola A, Montorfano, Gigliola, Berra, Bruno

2011

Overview

Background PUFAs 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. Methods Two 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. Results We 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. Conclusions Our 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.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Apoptosis - drug effects / Biomedical and Life Sciences / Breast cancer / Breast Neoplasms - enzymology / Breast Neoplasms - pathology / Cancer cells / Caspase 8 - metabolism / Cell Line, Tumor / Cell Membrane - drug effects / Cell Membrane - metabolism / Cell Proliferation - drug effects / Cell Survival - drug effects / Clinical Nutrition / Cytokines / Docosahexaenoic Acids - pharmacology / Eicosapentaenoic Acid - pharmacology / Epidermal Growth Factor - pharmacology / Fatty Acids, Omega-3 - pharmacology / Female / Gene expression / Health aspects / Humans / Life Sciences / Lipidology / Medical Biochemistry / Phospholipids - metabolism / Phosphorylation - drug effects / Physiological aspects / Proto-Oncogene Proteins c-bcl-2 - metabolism / Receptor, Epidermal Growth Factor - metabolism