title: Dietary supplementation with methylseleninic acid, but not selenomethionine, reduces spontaneous metastasis of Lewis lung carcinoma in mice.
abstract: The present study investigated the effects of dietary supplementation with methylseleninic acid (MSeA), in comparison with selenomethionine (SeMet), 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 SeMet at 2.5 mg selenium/kg for 4 weeks at which time they were injected intramuscularly or subcutaneously with 2.5 × 10(5)  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 when compared with the controls (p < 0.05) in both models; however, SeMet did not have such an 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) when compared with the controls. Selenomethionine did not affect any of the aforementioned measurements. These results demonstrate that MSeA reduces spontaneous metastasis of LLC in mice, perhaps through inhibition of the urokinase plasminogen activator system and reducing angiogenesis.
authors.affiliation: U.S. Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202, USA. lin.yan@ars.usda.gov
authors.forename: Lin
authors.initials: L
authors.lastname: Yan
authors.forename: Lana C
authors.initials: LC
authors.lastname: DeMars
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D045744:Cell Line, Tumor; D019587:Dietary Supplements; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D016566:Organoselenium Compounds / Q000008:administration & dosage*; D012645:Selenomethionine / Q000008:administration & dosage*; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D016566:Organoselenium Compounds; D042461:Vascular Endothelial Growth Factor A; D012645:Selenomethionine; C008493:methylselenic acid; D014568:Urokinase-Type Plasminogen Activator