Submitted to: International Journal of Cancer
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 4, 2011
Publication Date: July 3, 2012
Repository URL: http://handle.nal.usda.gov/10113/56800
Citation: Yan, L., Demars, L.C. 2012. Dietary supplementation with methylseleninic acid, but not selenomethionine, reduces spontaneous metastasis of Lewis lung carcinoma in mice. International Journal of Cancer. 131:1260-1266. Interpretive Summary: Selenium is a trace element essential to humans. Great attention has been given to its role in primary cancer prevention; however, relatively few studies have addressed the activity of selenium in secondary cancer prevention. Secondary cancer prevention refers to the prevention of malignant spread from a primary tumor to distant organs, which is the most devastating aspect of cancer, and its occurrence directly affects the prognosis and survival of cancer patients. Methylseleninic acid is a unique selenium compound that has been shown to be effective in primary cancer prevention. The present study investigated its effects on spontaneous metastasis of Lewis lung carcinoma in mice. We found that feeding mice a methylseleninic acid containing diet significantly decreased the number of tumors developed in the lungs in mice subcutaneously injected with cancer cells, and this reduction is accompanied with significant reduction in plasma concentrations of urokinase type plasminogen activator (an enzyme responsible for cancer invasion) and angiogenic biomarkers. These results demonstrate that Methylseleninic acid reduces spontaneous metastasis of Lewis lung carcinoma in mice, perhaps through inhibition of the urokinase plasminogen activator system and reducing angiogenesis, and it suggests that methylseleninic acid has a great potential to be used in secondary cancer prevention.
Technical Abstract: Dietary supplementation with methylseleninic acid reduces spontaneous metastasis of Lewis lung carcinoma in mice Lin Yan*, Lana C. DeMars The present study investigated the effects of dietary supplementation with methylseleninic acid (MSeA) on spontaneous metastasis of Lewis lung carcinoma (LLC) in male C57BL/6 mice using intramuscular and subcutaneous injection models. Mice were fed AIN93G control diet or that diet supplemented with MSeA or selenomethionine (SeMet) at 2.5 mg selenium/kg for 4 weeks at which time they were injected intramuscularly or subcutaneously with 2.5 x 105 viable LLC cells. Experiments were terminated 2 weeks later for mice injected intramuscularly or 2 weeks after surgical removal of primary tumors from mice subcutaneously injected with cancer cells. Dietary supplementation with MSeA significantly reduced pulmonary metastatic yield compared with the controls (P < 0.05) in both models; however, SeMet treatment was without effect. Supplementation with MSeA significantly decreased plasma concentrations of urokinase-type plasminogen activator (P < 0.05) and plasminogen activator inhibitor-1 (P < 0.05). Furthermore, MSeA significantly reduced plasma concentrations of vascular endothelial growth factor (P < 0.05), fibroblast growth factor basic (P < 0.05) and platelet-derived growth factor-BB (P < 0.05) compared with the controls. Selenomethionine did not affect any of the aforementioned variables. These results demonstrate that MSeA reduces spontaneous metastasis of LLC in mice, perhaps through inhibition of the urokinase plasminogen activator system and reducing angiogenesis.