Dietary Supplementation with Methylseleninic Acid Inhibits Mammary Tumorigenesis and Metastasis in Male MMTV-PyMT Mice

Biol Trace Elem Res. 2018 Jul;184(1):186-195. doi: 10.1007/s12011-017-1188-7. Epub 2017 Oct 14.

Abstract

Male breast cancer, which makes up approximately 1% of all breast cancers, is an aggressive disease with poor prognosis. We investigated the effects of dietary supplementation with selenium in the form of methylseleninic acid [(MSeA) 2.5 mg selenium/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). Dietary supplementation with MSeA, versus the control, resulted in a 72% reduction in tumor progression, a 46% reduction in both final volume and weight of mammary tumors, and a 70% reduction in the number of lung metastases. Mammary tumorigenesis in MMTV-PyMT mice, versus non-tumor-bearing wild-type mice, resulted in significant increases in concentrations of plasminogen activator inhibitor-1, urokinase plasminogen activator, monocyte chemotactic protein-1, and vascular endothelial growth factor, but not aromatase and estrogen, in the plasma. Concentrations of all variables mentioned above 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.

Keywords: MMTV-PyMT; Male; Mammary tumorigenesis; Metastasis; Selenium.

MeSH terms

  • Adiponectin / blood
  • Animals
  • Biomarkers / blood
  • Breast Neoplasms / blood
  • Breast Neoplasms / complications
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Transformation, Neoplastic / drug effects
  • Dietary Supplements
  • Female
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / etiology
  • Lung Neoplasms / pathology
  • Male
  • Mammary Neoplasms, Experimental / blood
  • Mammary Neoplasms, Experimental / drug therapy*
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Organoselenium Compounds / therapeutic use*

Substances

  • Adiponectin
  • Biomarkers
  • Organoselenium Compounds
  • methylselenic acid