Dataset Information

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.

SUBMITTER: Ford NA

PROVIDER: S-EPMC5024781 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Ford Nikki A NA Rossi Emily L EL Barnett Kelsey K Yang Peiying P Bowers Laura W LW Hidaka Brandon H BH Kimler Bruce F BF Carlson Susan E SE Shureiqi Imad I deGraffenried Linda A LA Fabian Carol J CJ Hursting Stephen D SD

Cancer prevention research (Philadelphia, Pa.) 20150622 9

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 (D ...[more]

PMID: 26100521

Similar Datasets

Project description:BACKGROUND:Omega-3 fatty acids from fish oil have been associated with beneficial cardiovascular effects, but their role in modifying cardiac structures and tissue characteristics in patients who have had an acute myocardial infarction while receiving current guideline-based therapy remains unknown. METHODS:In a multicenter, double-blind, placebo-controlled trial, participants presenting with an acute myocardial infarction were randomly assigned 1:1 to 6 months of high-dose omega-3 fatty acids (n=180) or placebo (n=178). Cardiac magnetic resonance imaging was used to assess cardiac structure and tissue characteristics at baseline and after study therapy. The primary study endpoint was change in left ventricular systolic volume index. Secondary endpoints included change in noninfarct myocardial fibrosis, left ventricular ejection fraction, and infarct size. RESULTS:By intention-to-treat analysis, patients randomly assigned to omega-3 fatty acids experienced a significant reduction of left ventricular systolic volume index (-5.8%, P=0.017), and noninfarct myocardial fibrosis (-5.6%, P=0.026) in comparison with placebo. Per-protocol analysis revealed that those patients who achieved the highest quartile increase in red blood cell omega-3 index experienced a 13% reduction in left ventricular systolic volume index in comparison with the lowest quartile. In addition, patients in the omega-3 fatty acid arm underwent significant reductions in serum biomarkers of systemic and vascular inflammation and myocardial fibrosis. There were no adverse events associated with high-dose omega-3 fatty acid therapy. CONCLUSIONS:Treatment of patients with acute myocardial infarction with high-dose omega-3 fatty acids was associated with reduction of adverse left ventricular remodeling, noninfarct myocardial fibrosis, and serum biomarkers of systemic inflammation beyond current guideline-based standard of care. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT00729430.

Project description:IntroductionPatients with diabetes and prediabetes are at increased risk of dyslipidemia and cardiovascular disease. To reduce this risk, statins and additional therapies may be considered. Omega-3 fatty acids offer an option to reduce triglycerides (TG) and potentially improve other lipid parameters, although products that contain docosahexaenoic acid (DHA) may increase low-density lipoprotein cholesterol (LDL-C) while eicosapentaenoic acid (EPA) does not. Prescription formulations include omega-3-acid mixtures (combination of predominantly EPA and DHA), and icosapent ethyl (high-purity prescription form of EPA ethyl ester); prescription omega-3 products are indicated as an adjunct to diet to reduce TGs in adult patients with severe hypertriglyceridemia at a dose of 4 g/day.MethodsThis was a retrospective analysis of records from a private endocrinology practice of patients who received omega-3-acid ethyl esters (OM3EE) (4 g/day) and were subsequently switched to icosapent ethyl (IPE; 4 g/day) due to the potential of OM3EE to raise LDL-C and/or cause gastrointestinal upset. Patient records were analyzed for LDL-C, TG, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and non-HDL-C measured before and after the switch to IPE.ResultsThe records of ten patients met the criteria for this analysis and were included. All patients had taken OM3EE for ≥1 year prior to their last lipid measurement before switching to IPE, and all had been taking IPE for >3 months at the time of their subsequent lipid measurement. Nine of the ten patients were on concomitant statin therapy throughout. Reductions in LDL-C, TC, and non-HDL-C were observed in eight patients, reductions or no changes in TG were observed in eight patients, and increases or no changes in HDL-C were observed in eight patients. No gastrointestinal adverse events were observed.ConclusionIn most patients with prediabetes or diabetes who switched from OM3EE to IPE, LDL-C and other lipid parameters improved. IPE was well tolerated.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets