Report

Breast Cancer Research and Treatment

, Volume 92, Issue 2, pp 187-195

First online:

Mechanisms of omega-3 fatty acid-induced growth inhibition in MDA-MB-231 human breast cancer cells

  • Patricia D. SchleyAffiliated withDepartment of Agricultural,Food and Nutritional Science, University of Alberta
  • , Humberto B. JijonAffiliated withDepartment of Medicine, Division of Gastroenterology, University of Alberta
  • , Lindsay E. RobinsonAffiliated withDepartment of Human Biology and Nutritional Sciences, University of Guelph
  • , Catherine J. FieldAffiliated withDepartment of Agricultural,Food and Nutritional Science, University of AlbertaDepartment of Agricultural, Food and Nutritional Science, University of Alberta, Email author 

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Summary

The omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), inhibit the growth of human breast cancer cells in animal models and cell lines, but the mechanism by which this occurs is not well understood. In order to explore possible mechanisms for the modulation of breast cancer cell growth by omega-3 fatty acids, we examined the effects of EPA and DHA on the human breast cancer cell line MDA-MB-231. Omega-3 fatty acids (a combination of EPA and DHA) inhibited the growth of MDA-MB-231 cells by 30–40% (p<0.05) in both the presence and absence of linoleic acid, an essential omega-6 fatty acid. When provided individually, DHA was more potent than EPA in inhibiting the growth of MDA-MB-231 cells (p<0.05). EPA and DHA treatment decreased tumor cell proliferation (p<0.05), as estimated by decreased [methyl−3H]-thymidine uptake and expression of proliferation-associated proteins (proliferating cell nuclear antigen, PCNA, and proliferation-related kinase, PRK). In addition, EPA and DHA induced apoptosis, as indicated by a loss of mitochondrial membrane potential, increased caspase activity and increased DNA fragmentation (p<0.05). Cells incubated with omega-3 fatty acids demonstrated decreased Akt phosphorylation, as well as NFκB DNA binding activity (p<0.05). The results of this study indicate that omega-3 fatty acids decrease cell proliferation and induce apoptotic cell death in human breast cancer cells, possibly by decreasing signal transduction through the Akt/NFκB cell survival pathway.

Keywords

Akt apoptosis breast cancer docosahexaenoic acid eicosapentaenoic acid MDA-MB-231 NFκB omega-3 fatty acid proliferation