Modulation of estrogen and progesterone receptor expression by fish oil and tamoxifen in 7,12 dimethyl benz(a) anthracene induced mammary carcinogenesis in female sprague dawely rats
Paper Details
Modulation of estrogen and progesterone receptor expression by fish oil and tamoxifen in 7,12 dimethyl benz(a) anthracene induced mammary carcinogenesis in female sprague dawely rats
Abstract
Cancer remains a primary global health challenge characterized by uncontrolled cellular proliferation and significant mortality. Within this landscape, breast cancer represents one of the most prevalent and hormone-dependent malignancies, contributing substantially to cancer-related deaths. While endocrine therapy with tamoxifen is a standard treatment for estrogen receptor-positive (ER+) breast cancer, its efficacy is often hampered by dose-associated toxicity and inconsistent outcomes. This study evaluates the potential of fish oil, rich in omega-3 polyunsaturated fatty acids, as an adjunct to tamoxifen in modulating hormonal imbalance and estrogen/progesterone receptor (ER/PR) expression. A 7,12-dimethylbenz(a)anthracene (DMBA)–induced mammary tumor model was established in female Sprague Dawley rats to assess the effects of fish oil alone and in combination with low and high-dose tamoxifen. Plasma estradiol and progesterone levels were quantified via ELISA, while ER/PR expression in mammary tissues was evaluated by immunohistochemistry. DMBA induction significantly increased ER and PR expression, indicating hormonal dysregulation. Fish oil treatment alone produced a moderate reduction in receptor expression. However, the combination of fish oil with tamoxifen markedly suppressed ER and PR levels. Notably, the fish oil low-dose tamoxifen combination produced effects comparable to the high-dose combination, suggesting that fish oil may enhance tamoxifen efficacy and allow effective endocrine regulation with a lower drug dose and potentially reduced toxicity. Fish oil maintained physiological hormone levels in control animals. In conclusion, fish oil enhances the endocrine-modulating effects of tamoxifen and may serve as a beneficial supplementary strategy to improve therapeutic efficacy while potentially minimizing adverse effects.
Bidinotto LT, de Cicco RL, Vanegas JE, Santucci-Pereira J, Vanden Heuvel JP, Washington S. 2012. Fish oil alters tamoxifen-modulated expression of mRNAs that encode genes related to differentiation, proliferation, metastasis, and immune response in rat mammary tumors. Nutrition and Cancer 64, 991–999.
Bougnoux P, Hajjaji N, Ferrasson MN, Giraudeau B, Couet C, Le Floch O. 2009. Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: A phase II trial. British Journal of Cancer 101, 1978–1985.
Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I. 2024. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians 74, 229–263.
Cao W, Ma Z, Rasenick MM, Yeh S, Yu J. 2012. N-3 polyunsaturated fatty acids shift estrogen signaling to inhibit human breast cancer cell growth. PLoS ONE 7, e52838.
Fabian CJ, Kimler BF, Hursting SD. 2015. Omega-3 fatty acids for breast cancer prevention and survivorship. Breast Cancer Research 17, 62.
Freihat O, Sipos D, Kovacs A. 2025. Global burden and projections of breast cancer incidence and mortality to 2050: A comprehensive analysis of GLOBOCAN data. Frontiers in Public Health 13, 1622954.
Manni A, El-Bayoumy K, Skibinski CG, Thompson HJ, Santucci-Pereira J, Bidinotto LT, et al. 2015. Combination of antiestrogens and omega-3 fatty acids for breast cancer prevention. BioMed Research International 2015, 638645.
Manni A, Richie JP Jr, Xu H, Washington S, Aliaga C, Bruggeman R. 2020. Influence of omega-3 fatty acids on endocrine signaling and mammary tumor growth in experimental breast cancer. Breast Cancer Research and Treatment 180, 351–362.
Manni A, Xu H, Washington S, Aliaga C, Cooper TK, Richie JP Jr. 2010. The impact of fish oil on the chemopreventive efficacy of tamoxifen against development of N-methyl-N-nitrosourea-induced rat mammary carcinogenesis. Cancer Prevention Research 3, 322–330.
National Cancer Institute. 2026. Low dose tamoxifen with or without omega-3 fatty acids for breast cancer risk reduction (NCT06195306). ClinicalTrials.gov.
Rengarajan T, Rajendran P, Nandakumar N, Lokeshkumar B, Rajendran P, Nishigaki I. 2015. Exposure to polycyclic aromatic hydrocarbons and risk of breast cancer. Environmental Toxicology and Pharmacology 40, 605–614.
Rodgers KM, Udesky JO, Rudel RA, Brody JG. 2018. Environmental chemicals and breast cancer: An updated review of epidemiological literature informed by biological mechanisms. Environmental Research 160, 152–182.
Subbaramaiah K, Iyengar NM, Dannenberg AJ. 2019. Targeting the white adipose tissue inflammation-aromatase axis for breast cancer prevention. Cancer Prevention Research 12, 721–728.
Yager JD, Davidson NE. 2006. Estrogen carcinogenesis in breast cancer. The New England Journal of Medicine 354, 270–282.
Caroline Paul Mari, Mirunalini Sankaran*, 2026. Modulation of estrogen and progesterone receptor expression by fish oil and tamoxifen in 7,12 dimethyl benz(a) anthracene induced mammary carcinogenesis in female sprague dawely rats. J. Biodiv. Environ. Sci., 29(2), 22-28.
Copyright © 2026 by the Authors. This article is an open access article and distributed under the terms and conditions of the Creative Commons Attribution 4.0 (CC BY 4.0) license.