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

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

Author information

1
Department of Nutritional Sciences, University of Texas, Austin, Texas.
2
Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina.
3
Department of General Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
4
Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, Kansas.
5
Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, Kansas.
6
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
7
Division of Hematology-Oncology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
8
Department of Nutritional Sciences, University of Texas, Austin, Texas. Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina. hursting@email.unc.edu.

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.

PMID:
26100521
PMCID:
PMC5024781
DOI:
10.1158/1940-6207.CAPR-15-0018
[Indexed for MEDLINE]
Free PMC Article

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