Abstract 1401: Dietary selenium and metastasis in a mouse model

Abstract

Abstract The skeleton is a common site for breast cancer metastasis. Once breast cancer cells enter the bone microenvironment, they alter the homeostasis of the bone remodeling system in favor of osteoclasts, which results in osteolysis. Breast cancer cells induce an osteoblast inflammatory response resulting in the production of IL-6, IL-8, MCP-1, and COX-2, known to promote osteoclastogenesis. Therefore, down-regulation of the inflammatory response of the osteoblasts brought about by breast cancer cells may reduce the activation of osteoclasts and decrease osteolysis. IL-6, MCP-1, COX-2 are regulated by a common transcription factor, NF-κB which is sensitive to intracellular redox status; its activation can be inhibited by cellular antioxidant enzymes. Two major antioxidant enzymes, glutathione peroxidase and thioredoxin reductase are selenoenzymes. Their dependence on selenium (Se) offers a way to increase their expression and activity, block NF-κB activation and thus inhibit the expression of its target genes. The hypothesis was that inhibition of NF-κB through dietary selenium would prevent the osteoblast inflammatory response and metastasis. To test the effect of dietary selenium in breast cancer progression, one of five diets: three selenium supplementation diets (sodium selenite, selenomethionine, and methylseleninic acid) or a selenium-deficient or a selenium adequate diet was fed to Balb/c mice for 3 months before inoculation of a metastatic breast cancer cell line 4T1.2luc into the mammary gland. The growth and metastasis of the tumors were followed by IVIS imaging. After 4 weeks, organs were collected and prepared for Q-PCR analysis of the luciferase gene as an indicator of metastatic burden. There was no significant difference in the development or growth of the primary breast tumor and the metastatic patterns between mice receiving the selenium-deficient or selenium-adequate diets. On the other hand, selenium supplementation diets were shown to affect breast cancer progression differently. Mice with sodium selenite supplementation developed the most metastasis (15/15) and showed higher incidence of breast cancer kidney and bone metastasis. The selenomethionine supplementation diet (3ppm) reduced breast cancer primary tumor growth and decreased overall tumor burden in major organs, such as lung, liver, kidney and femur. Taken together, this study showed that dietary selenium affected tumor growth and metastasis and that the selenomethionine supplementation diet offered the most protective effect on breast cancer progression. Support: American Institute for Cancer Research with supplemental support from the National Foundation for Cancer Research. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1401. doi:1538-7445.AM2012-1401