Dietary selenium supplementation modifies breast tumor growth and metastasis

Int J Cancer. 2013 Nov;133(9):2054-64. doi: 10.1002/ijc.28224. Epub 2013 Jul 6.

Abstract

The survival rate for breast cancer drops dramatically once the disease progresses to the metastatic stage. Selenium (Se) is an essential micronutrient credited with having high anticancer and chemopreventive properties. In our study, we investigated if dietary Se supplementation modified breast cancer development in vivo. Three diets supplemented with sodium selenite, methylseleninic acid (MSA) or selenomethionine (SeMet), as well as a Se-deficient and a Se-adequate diet were fed to mice before mammary gland inoculation of 4T1.2 cells. The primary tumor growth, the numbers of cancer cells present in lungs, hearts, livers, kidneys and femurs and several proinflammatory cytokines were measured. We found that inorganic selenite supplementation provided only short-term delay of tumor growth, whereas the two organic SeMet and MSA supplements provided more potent growth inhibition. These diets also affected cancer metastasis differently. Mice fed selenite developed the most extensive metastasis and had an increased incidence of kidney and bone metastasis. On the other hand, mice fed the SeMet diet showed the least amount of cancer growth at metastatic sites. The MSA diet also provided some protection against breast cancer metastasis although the effects were less significant than those of SeMet. The cytokine profiles indicated that serum levels of interlukin-2, interleukin-6, interferon γ and vascular endothelial growth factor were elevated in SeMet-supplemented mice. There was no significant difference in tumor growth and the patterns of metastasis between the Se-deficient and Se-adequate groups. Our data suggest that organic Se supplementation may reduce/delay breast cancer metastasis, while selenite may exacerbate it.

Keywords: breast cancer; dietary nutrient supplementation; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Bone Neoplasms / diet therapy
  • Bone Neoplasms / secondary*
  • Dietary Supplements*
  • Female
  • Flow Cytometry
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-2 / genetics
  • Interleukin-2 / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Kidney Neoplasms / diet therapy
  • Kidney Neoplasms / secondary*
  • Lung Neoplasms / diet therapy
  • Lung Neoplasms / secondary*
  • Mammary Neoplasms, Animal / diet therapy
  • Mammary Neoplasms, Animal / pathology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Organoselenium Compounds / administration & dosage
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Selenomethionine / administration & dosage
  • Sodium Selenite / administration & dosage
  • Tumor Cells, Cultured

Substances

  • Interleukin-2
  • Interleukin-6
  • Organoselenium Compounds
  • RNA, Messenger
  • Interferon-gamma
  • Selenomethionine
  • methylselenic acid
  • Sodium Selenite