Breast Cancer Genetic and Molecular Subtype Impacts Response to Omega-3 Fatty Acid Ethyl Esters

Nutr Cancer. Aug-Sep 2016;68(6):1021-33. doi: 10.1080/01635581.2016.1192199. Epub 2016 Jul 1.


Epidemiological studies have correlated frequent omega-3 (n-3) fatty acid consumption with a lower risk for breast cancer; however, recent prospective studies have been less conclusive. Efforts in the preventive setting have focused on the use of n-3 fatty acids, and the pharmaceutical ethyl esters (EE) of these natural compounds, for high-risk patient populations. Limited understanding of specific mechanisms by which these agents function has hampered identification of the cancer subtype(s) that would gain the greatest therapeutic benefit. In this study, we investigated the in vitro effects of n-3 EEs in four distinct breast cancer subtypes and explored how they affect not only breast cancer cell survival but also modulate the nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) and peroxisome proliferator-activated receptor gamma signaling pathways. Similar to the high variance in response observed in human studies, we found that the effectiveness of n-3 EEs depends on the molecular characteristics of the MCF-7, CAMA-1, MDA-MB-231, and SKBR3 breast cancer cell lines and is closely associated with the suppression of NF-κB. These data strongly suggest that the use of n-3 fatty acids and their pharmaceutical ether esters in the prevention and therapeutic setting should be guided by specific tumor characteristics.

MeSH terms

  • Anticarcinogenic Agents / metabolism*
  • Anticarcinogenic Agents / therapeutic use
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / prevention & control
  • Cell Line, Tumor
  • Cell Survival
  • Colony-Forming Units Assay
  • Dietary Supplements
  • Docosahexaenoic Acids / metabolism*
  • Docosahexaenoic Acids / therapeutic use
  • Drug Combinations
  • Eicosapentaenoic Acid / metabolism*
  • Eicosapentaenoic Acid / therapeutic use
  • Esters / metabolism
  • Esters / therapeutic use
  • Fatty Acids, Omega-3 / metabolism*
  • Fatty Acids, Omega-3 / therapeutic use
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Humans
  • Kinetics
  • Mutation
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • PPAR gamma / antagonists & inhibitors
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Polymorphism, Single Nucleotide*
  • Signal Transduction


  • Anticarcinogenic Agents
  • Drug Combinations
  • Esters
  • Fatty Acids, Omega-3
  • NF-kappa B
  • Neoplasm Proteins
  • PPAR gamma
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • Omacor