Influence of omega‐3 fatty acids on Tamoxifen‐induced suppression of rat mammary carcinogenesis

Manni, Andrea; Richie, John P.; Xu, Haifang; Washington, Sharlene; Aliaga, César; Bruggeman, Richard; Cooper, Timothy K.; Prokopczyk, Bogdan; Trushin, Neil; Das, Arunangshu; Liao, Jason; El‐Bayoumy, Karam

doi:10.1002/ijc.28490

Cited by 17 publications

(16 citation statements)

References 16 publications

(54 reference statements)

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“…Because such compounds are to be used in healthy women, they have to be safe without significant side effects. Our preclinical data in rodent models of mammary carcinogenesis have shown that fish oil, rich in omega-3FA, potentiated the chemopreventive effect of tamoxifen (5,6). Furthermore, our signaling (7), genomic (8), and proteomic (9) studies suggested complementarity in the mechanism of antitumor action of tamoxifen and n-3FA.…”

Section: Introductionmentioning

confidence: 60%

Influence of Obesity on Breast Density Reduction by Omega-3 Fatty Acids: Evidence from a Randomized Clinical Trial

Sandhu

Schetter

Liao

et al. 2016

Cancer Prevention Research

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Preclinical data indicate that omega-3 fatty acids (n-3FA) potentiate the chemopreventive effect of the antiestrogen (AE) tamoxifen against mammary carcinogenesis. The role of n-3FA in breast cancer prevention in humans is controversial. Preclinical and epidemiologic data suggest that n-3FA may be preferentially protective in obese subjects. To directly test the protective effect of n-3FA against breast cancer, we conducted a 2-year, open-label randomized clinical trial in 266 healthy postmenopausal women (50% normal weight, 30% overweight, 20% obese) with high breast density (BD; ≥25%) detected on their routine screening mammograms. Eligible women were randomized to one of the following five groups (i) no treatment, control; (ii) raloxifene 60 mg; (iii) raloxifene 30 mg; (iv) n-3FA lovaza 4 g; and (v) lovaza 4 g plus raloxifene 30 mg. The 2-year change in BD, a validated biomarker of breast cancer risk, was the primary endpoint of the study. In subset analysis, we tested the prespecified hypothesis that body mass index (BMI) influences the relationship between plasma n-3FA on BD. While none of the interventions affected BD in the intention-to-treat analysis, increase in plasma DHA was associated with a decrease in absolute breast density but only in participants with BMI >29. Our results suggest that obese women may preferentially experience breast cancer risk reduction from n-3FA administration.

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Section: Introductionmentioning

confidence: 60%

Influence of Obesity on Breast Density Reduction by Omega-3 Fatty Acids: Evidence from a Randomized Clinical Trial

Sandhu

Schetter

Liao

et al. 2016

Cancer Prevention Research

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“…mega-3 PUFAs signaling via GPR120 and Toll-like receptor 4 (TLR4) utilize the same NFκB and JNK pathways as TNFα so they could potentially interfere with these proliferative signals 19 , 34 . Among dietary fat subtypes, ω-3 PUFAs offer the most promise for reducing the risk of carcinogenesis 18 , 21 . So we tested whether HFD supplementation with ω-3 PUFAs derived from fish oil (FOD, fish oil diet) could reduce inflammation in the mammary and perigonadal fat pads of obese OVX mice in the absence of tumor formation.…”

Section: Resultsmentioning

confidence: 99%

Omega-3 fatty acids reduce obesity-induced tumor progression independent of GPR120 in a mouse model of postmenopausal breast cancer

et al. 2014

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Obesity and inflammation are both risk factors for a variety of cancers including breast cancer in postmenopausal women. Intake of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) decreases the risk of breast cancer, and also reduces obesity-associated inflammation and insulin resistance, but whether the two effects are related is currently unknown. We tested this hypothesis in a postmenopausal breast cancer model using ovariectomized (OVX), immune-competent female mice with orthotopically injected with Py230 mammary tumor cells. Obesity, whether triggered genetically or by high-fat diet (HFD) feeding, increased inflammation in the mammary fat pad and promoted mammary tumorigenesis. The presence of tumor cells in the mammary fat pad further enhanced the local inflammatory milieu. TNF-α was the most highly up-regulated cytokine in the obese mammary fat pad, and we observed that TNF-α dose-dependently stimulated Py230 cell growth in vitro. An ω-3 PUFA-enriched HFD (referred to as fish oil diet, FOD) reduced inflammation in the obese mammary fat pad in the absence of tumor cells and inhibited Py230 tumor growth in vivo. Although some anti-inflammatory effects of ω-3 PUFAs were previously shown to be mediated by the G protein-coupled receptor 120 (GPR120), the FOD reduced Py230 tumor burden in GPR120 deficient mice to a similar degree as observed in WT mice, indicating that effect of FOD to reduce tumor growth does not require GPR120 in the host mouse. Instead, in vitro studies demonstrated that ω-3 PUFAs act directly on tumor cells to activate JNK, inhibit proliferation and induce apoptosis. Our results show that obesity promotes mammary tumor progression in this model of postmenopausal breast cancer and that ω-3 PUFAs inhibit mammary tumor progression in obese mice, independent of GPR120. Keywords: obesity, mammary tumors, inflammation, postmenopausal breast cancer,ω-3 PUFAs, GPR120

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“…It is perceived that the observed effects may be attributed to their influence on gene expression, transcription factors, and suppression of neoplastic stimulations, and to their ability to influence the production of ROS, cell metabolism and induce apoptosis (24,25,26). Fatty acids were also shown to enhance the effectiveness of standard chemo-or radiotherapy (27,28). On the contrary, SFA and MUFA can stimulate tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Seasonal variation in biopharmaceutical activity and fatty acid content of endemic Fucus virsoides algae from Adriatic Sea

Grozdanić¹,

Zdunić²,

Šavikin³

et al. 2019

Acta Poloniae Pharmaceutica - Drug Research

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Fucus virsoides J. Agardh is an endemic brown alga found only in the Adriatic Sea. Other members of the Fucus genus have shown anticancer potential, namely F. vesiculosus L. (1) and its most active component fucoidan. Algae from the Fucus genus are rich in active biological compounds such as polysaccharides, polyphenols, fatty acids and vitamins (2). Fucoidans have been documented for numerous biological activities such as antiviral, anti-inflammatory, anticoagulant, anti-angiogenic, immunomodulatory, and anti-adhesive activities (3, 4). The biological effects of these compounds can vary due to chemical structure differences that depend on the species from which they have been isolated (3). The anticancer or antidiabetic properties of Fucus virsoides have not been investigated in detail. Polyphenols, secondary metabolites, have been studied for their role in the prevention of cancer, diabetes, cardiovascular diseases, osteoporosis, and neurodegenerative diseases. Polyphenols exert antioxidant, free radical scavenging activities; they

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Influence of omega‐3 fatty acids on Tamoxifen‐induced suppression of rat mammary carcinogenesis

Cited by 17 publications

References 16 publications

Influence of Obesity on Breast Density Reduction by Omega-3 Fatty Acids: Evidence from a Randomized Clinical Trial

Influence of Obesity on Breast Density Reduction by Omega-3 Fatty Acids: Evidence from a Randomized Clinical Trial

Omega-3 fatty acids reduce obesity-induced tumor progression independent of GPR120 in a mouse model of postmenopausal breast cancer

Seasonal variation in biopharmaceutical activity and fatty acid content of endemic Fucus virsoides algae from Adriatic Sea

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