Omega-3-Acid Ethyl Esters Block the Protumorigenic Effects of Obesity in Mouse Models of Postmenopausal Basal-like and Claudin-Low Breast Cancer

Cancer Prev Res (Phila). 2015 Sep;8(9):796-806. doi: 10.1158/1940-6207.CAPR-15-0018. Epub 2015 Jun 22.

Abstract

Obesity induces chronic inflammation and is an established risk and progression factor for triple-negative breast cancers, including basal-like (BL) and claudin-low (CL) subtypes. We tested the effects of dietary supplementation with ethyl esters of the marine-derived anti-inflammatory omega-3 fatty acids eicosapentaenoic and docosahexaenoic acid (EPA+DHA; Lovaza) on growth of murine BL and CL mammary tumors. Female ovariectomized C57BL/6 mice were fed a control diet or a diet-induced obesity (DIO) diet with or without EPA+DHA (0.025%, resulting in blood levels of EPA and DHA comparable with women taking Lovaza 4 g/d) for 6 weeks. All mice were then orthotopically injected with Wnt-1 cells (a BL tumor cell suspension derived from MMTV-Wnt-1 transgenic mouse mammary tumors) or M-Wnt cells (a CL tumor cell line cloned from the Wnt-1 tumor cell suspension). Mice were killed when tumors were 1 cm in diameter. EPA+DHA supplementation did not significantly affect Wnt-1 or M-Wnt mammary tumor growth in normoweight control mice. However, EPA+DHA supplementation in DIO mice reduced growth of Wnt-1 and M-Wnt tumors; reduced leptin:adiponectin ratio and proinflammatory eicosanoids in the serum; improved insulin sensitivity; and decreased tumoral expression of COX-2 and phospho-p65. Thus, EPA+DHA supplementation in mouse models of postmenopausal BL and CL breast cancer offsets many of the protumorigenic effects of obesity. These preclinical findings, in combination with results from parallel biomarker studies in women, suggest that EPA+DHA supplementation may reduce the burden of BL and CL breast cancer in obese women.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / blood
  • Animals
  • Body Composition
  • Cell Line, Tumor
  • Claudin-1 / metabolism*
  • Cyclooxygenase 2 / metabolism
  • Eicosanoids / blood
  • Erythrocytes / cytology
  • Esters / chemistry
  • Fatty Acids, Omega-3 / chemistry*
  • Female
  • Glucose Tolerance Test
  • Inflammation
  • Leptin / blood
  • Mammary Neoplasms, Animal / metabolism*
  • Mammary Neoplasms, Experimental / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Obesity / genetics*
  • Obesity / metabolism
  • Pilot Projects
  • Postmenopause
  • Transcription Factor RelA / metabolism
  • Wnt1 Protein / metabolism

Substances

  • Adiponectin
  • Claudin-1
  • Cldn1 protein, mouse
  • Eicosanoids
  • Esters
  • Fatty Acids, Omega-3
  • Leptin
  • Transcription Factor RelA
  • Wnt1 Protein
  • Wnt1 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2