Fish oil contains two major marine omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), that have been reported to have chemopreventive effects in breast cancer cells and animal models of breast cancer. Fish oil has been found to prevent DNA damage and significantly reduce proliferation in precancerous tissues. Fish oil has also been found to inhibit early stages of mammary tumor development in a mouse models of HER-2/neu overexpressing (HER2+), triple negative (ER-/PR-/HER2-), and hormone receptor positive (ER+/PR+) breast cancer.
Fatty fish consumption has been shown to be associated with reduced risk of breast cancer and improved survival in women. Fish oil reduced bone metastasis in a mouse model of triple negative breast cancer in one study. Now a new study has elucidated the mechanism of action by which DHA inhibits ER+/PR+ breast cancer cell growth in breast cancer cells and a mouse model of breast cancer.
Fish oil supplements are not recommended during chemotherapy
Marine fatty acids have been found to enhance the therapeutic effects of chemotherapy drugs such as Adriamycin and Taxol. However, while consumption of fatty fish and other sources of omega-3 fats may be beneficial during chemotherapy, fish oil supplements could be harmful. A study published in 2011 (see Mesenchymal Stem Cells Induce Resistance to Chemotherapy through the Release of Platinum-Induced Fatty Acids below), reported that the fatty acids 12-oxo-5,8,10-heptadecatrienoic acid and hexadeca-4,7,10,13-tetraenoic acid found in some fish oil supplements induce resistance to a broad spectrum of chemotherapy drugs. Tumor-bearing mice injected with modest amounts of fish oil containing these fatty acids became insensitive to chemotherapy. Unfortunately, consumers are not in a position to know which fish oil supplements incorporate these two unwanted fatty acids.
In addition, there is some evidence that fish oil supplements taken during Adriamycin chemotherapy do not prevent heart damage and might actually promote it. Adriamycin and other anthracycline chemotherapy can cause cardiomyopathy, damage to the heart muscle that weakens its ability to pump and can lead to heart failure. Herceptin, used to treat HER2+ breast cancer, can also cause heart damage. Since omega-3 fatty acids have been found to reduce symptoms of heart failure in patients with traditional cardiovascular disease, some researchers have suggested that fish oil might have a role in protecting cancer patients from Adriamycin-induced cardiomyopathy. However, fish oil supplements might actually increase the risk of Adriamycin-induced chemotherapy, according to one 2012 study (see Dietary Omega-3 Supplementation Exacerbates Left Ventricular Dysfunction in an Ovine Model of Anthracycline-Induced Cardiotoxicity below). In the study, merino sheep given fish oil displayed greater signs of anthracycline cardiotoxicity than control sheep.
Latest research finds fish oil reduces metastasis
The study referenced at the beginning of this news story was designed to investigate the relationship between the marine omega-3 fatty acid DHA and β-catenin, one of the key components of the Wnt signaling pathway. The Wnt signaling pathway sends β-catenin into the cell nucleus to activate the epithelial-to-mesenchymal cell transitions that cancer cells undergo in the process of becoming capable of metastasis. Inhibition of β-catenin signaling appears to play a central role in the anticancer activity of certain micronutrients.
In the first part of the study, 4T1 mouse mammary cancer cells and ER+/PR+ MCF-7 human breast cells were exposed to DHA. The 4T1 line is a highly aggressive tumor cell line that can spontaneously metastasize from the primary mammary gland tumor to distant sites. DHA was found to inhibit cell growth strongly, inducing G1 cell cycle arrest in cell lines. DHA was found to reduce the expression of β-catenin, cyclinD1 and other genes involved in cancer growth and progression.
In the second part of the study, mice bearing 4T1 mammary tumors were divided into groups that were fed a either standard diet or a 5% fish oil-supplemented diet for 30 days. The fish oil diet was found to significantly reduce tumor growth by inhibiting cancer cell proliferation and inducing apoptosis (programmed cell death). The fish oil diet was shown to induce down-regulation of β-catenin in tumor tissues. The mice on the fish oil-supplemented diet also had decreased lung metastases. The authors conclude the findings suggest that DHA produces its anticancer effects through downregulation of Wnt/β-catenin signaling.
Please see our article on recommended fatty fish for more information on sources of marine omega-3 fats.