title: Omega-3-Acid Ethyl Esters Block the Protumorigenic Effects of Obesity in Mouse Models of Postmenopausal Basal-like and Claudin-Low Breast Cancer.
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.
authors.affiliation: Department of Nutritional Sciences, University of Texas, Austin, Texas.
authors.forename: Nikki A
authors.initials: NA
authors.lastname: Ford
authors.affiliation: Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Rossi
authors.affiliation: Department of Nutritional Sciences, University of Texas, Austin, Texas.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Barnett
authors.affiliation: Department of General Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Peiying
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Laura W
authors.initials: LW
authors.lastname: Bowers
authors.affiliation: Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Brandon H
authors.initials: BH
authors.lastname: Hidaka
authors.affiliation: Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Bruce F
authors.initials: BF
authors.lastname: Kimler
authors.affiliation: Department of Dietetics and Nutrition, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Carlson
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Imad
authors.initials: I
authors.lastname: Shureiqi
authors.affiliation: Department of Nutritional Sciences, University of Texas, Austin, Texas.
authors.forename: Linda A
authors.initials: LA
authors.lastname: deGraffenried
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Fabian
authors.affiliation: Department of Nutritional Sciences, University of Texas, Austin, Texas. Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina. hursting@email.unc.edu.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Hursting
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D001823:Body Composition; D045744:Cell Line, Tumor; D062445:Claudin-1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015777:Eicosanoids / Q000097:blood; D004912:Erythrocytes / Q000166:cytology; D004952:Esters / Q000737:chemistry; D015525:Fatty Acids, Omega-3 / Q000737:chemistry*; D005260:Female; D005951:Glucose Tolerance Test; D007249:Inflammation; D020738:Leptin / Q000097:blood; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D010865:Pilot Projects; D017698:Postmenopause; D051996:Transcription Factor RelA / Q000378:metabolism; D051155:Wnt1 Protein / Q000378:metabolism
chemical_list: D052242:Adiponectin; D062445:Claudin-1; C568113:Cldn1 protein, mouse; D015777:Eicosanoids; D004952:Esters; D015525:Fatty Acids, Omega-3; D020738:Leptin; D051996:Transcription Factor RelA; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2