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

H. Chung, Y. S. Lee, R. Mayoral, D. Y. Oh, J. T. Siu, N. J. Webster, D. D. Sears, J. M. Olefsky, L. G. Ellies

Research output: Contribution to journalArticle

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Abstract

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, immune-competent female mice 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. Tumor necrosis factor-alpha (TNF-α) was the most highly upregulated 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 wild-type mice, indicating that the 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 c-Jun N-terminal kinase, 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, independent of GPR120, inhibit mammary tumor progression in obese mice.

Original languageEnglish (US)
Pages (from-to)3504-3513
Number of pages10
JournalOncogene
Volume34
Issue number27
DOIs
StatePublished - Jul 1 2015
Externally publishedYes

Fingerprint

Omega-3 Fatty Acids
G-Protein-Coupled Receptors
Obesity
Breast Neoplasms
Breast
Fish Oils
Adipose Tissue
Neoplasms
Inflammation
High Fat Diet
Diet
Growth
Tumor Necrosis Factor-alpha
Obese Mice
JNK Mitogen-Activated Protein Kinases
Tumor Burden
Unsaturated Fatty Acids
Insulin Resistance
Carcinogenesis
Anti-Inflammatory Agents

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Chung, H., Lee, Y. S., Mayoral, R., Oh, D. Y., Siu, J. T., Webster, N. J., ... Ellies, L. G. (2015). Omega-3 fatty acids reduce obesity-induced tumor progression independent of GPR120 in a mouse model of postmenopausal breast cancer. Oncogene, 34(27), 3504-3513. https://doi.org/10.1038/onc.2014.283

Omega-3 fatty acids reduce obesity-induced tumor progression independent of GPR120 in a mouse model of postmenopausal breast cancer. / Chung, H.; Lee, Y. S.; Mayoral, R.; Oh, D. Y.; Siu, J. T.; Webster, N. J.; Sears, D. D.; Olefsky, J. M.; Ellies, L. G.

In: Oncogene, Vol. 34, No. 27, 01.07.2015, p. 3504-3513.

Research output: Contribution to journalArticle

Chung, H, Lee, YS, Mayoral, R, Oh, DY, Siu, JT, Webster, NJ, Sears, DD, Olefsky, JM & Ellies, LG 2015, 'Omega-3 fatty acids reduce obesity-induced tumor progression independent of GPR120 in a mouse model of postmenopausal breast cancer', Oncogene, vol. 34, no. 27, pp. 3504-3513. https://doi.org/10.1038/onc.2014.283
Chung, H. ; Lee, Y. S. ; Mayoral, R. ; Oh, D. Y. ; Siu, J. T. ; Webster, N. J. ; Sears, D. D. ; Olefsky, J. M. ; Ellies, L. G. / Omega-3 fatty acids reduce obesity-induced tumor progression independent of GPR120 in a mouse model of postmenopausal breast cancer. In: Oncogene. 2015 ; Vol. 34, No. 27. pp. 3504-3513.
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