Dietary supplementation with methylseleninic acid inhibits mammary tumorigenesis and metastasis in male MMTV-PyMT mice

Authors: Sundaram, Sneha; Yan, Lin

Submitted to: Biological Trace Element Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/3/2017
Publication Date: 10/14/2017
Publication URL: http://handle.nal.usda.gov/10113/5852204
Citation: Sundaram, S., Yan, L. 2017. Dietary supplementation with methylseleninic acid inhibits mammary tumorigenesis and metastasis in male MMTV-PyMT mice. Biological Trace Element Research. https://doi.org/10.1007/s12011-017-1188-7.

Interpretive Summary: Male breast cancer, which makes up approximately 1% of all breast cancer, is an aggressive disease with poor prognosis. Successes in prevention and treatment of male breast cancer are far less compared to that of female breast cancer due to a lack of research focused on male breast cancer. Selenium is an essential nutrient to humans with demonstrated capability of cancer prevention. We investigated the effect of the selenium compound, methylseleninic acid (MSeA), on breast cancer development and growth in a mouse model of male breast cancer. We found that consumption of a diet supplemented with MSeA inhibited the growth of breast tumors, reduced their spread to the lungs, and reduced levels of cancer-promoting chemicals in the body. Our findings clearly demonstrated that MSeA is preventive against male breast cancer in this mouse model. Findings from our study provide further evidence to the benefits of selenium in health promotion and disease prevention.

Technical Abstract: Male breast cancer, which makes up approximately 1% of all breast cancer, is an aggressive disease with poor prognosis. We investigated the effects of dietary supplementation with selenium in the form of methylseleninic acid (MSeA, 4.0 mg MSeA/kg) on mammary tumorigenesis in male MMTV-PyMT mice. The mammary tumor latency was 14.6 weeks for the MSeA-fed group and 13.8 weeks for the controls fed the AIN93G diet (p < 0.05). MSeA supplementation significantly reduced mammary tumor progression by 72%, mammary tumor weight by 46%, and the number of lung metastases by 70% compared to the controls. Mammary tumorigenesis in MMTV-PyMT mice, compared to non-tumor-bearing wild-type mice, resulted in significant increases in plasma concentrations of plasminogen activator inhibitor-1, urokinase plasminogen activator, monocyte chemotactic protein-1, and vascular endothelial growth factor, but not aromatase and estrogen. Concentrations of all aforementioned variables in both plasma and mammary tumors were lower in MSeA-fed mice. Mammary tumorigenesis reduced plasma levels of adiponectin compared to non-tumor-bearing controls. Adiponectin concentrations in mammary tumors, but not in plasma, were higher in MSeA-fed mice than in controls. In summary, dietary supplementation with selenium in the form of MSeA inhibits mammary tumorigenesis and its pulmonary metastasis in male MMTV-PyMT mice. These data indicate that MSeA may be useful in prevention of male breast cancer.