title: Consumption of a high-fat diet abrogates inhibitory effects of methylseleninic acid on spontaneous metastasis of Lewis lung carcinoma in mice.
abstract: We investigated the effect of dietary supplementation with selenium on spontaneous metastasis of Lewis lung carcinoma in mice fed a high-fat diet. Mice were fed a low-fat diet or that diet modified with 45% of calories from corn oil and supplemented with 0 or 2.5mg selenium/4029 kcal as methylseleninic acid. After 6 weeks, mice were each injected 2.5 × 10(5) Lewis lung carcinoma cells subcutaneously. The resulting primary tumor was removed surgically 10 days later; the experiment was terminated after an additional 10 days. High-fat feeding increased pulmonary metastases by 17% compared to the low-fat diet (P < 0.01). Selenium supplementation reduced the metastases by 11% compared to nonsupplemented controls (P < 0.05); the reduction was less for animals fed the high-fat diet (5%) than for those fed the low-fat diet (18%). Supplemental Se lowered plasma concentrations of proteases (urokinase plasminogen activator, P < 0.01; matrix metalloproteinase-9, P < 0.05) and angiogenic factors (vascular endothelial growth factor, P < 0.01; tissue inhibitor of metalloproteinase-1, P < 0.01) compared to nonsupplemented controls. High-fat feeding increased plasma concentrations of adipokines plasminogen activator inhibitor-1, monocyte chemotactic protein-1, tumor necrosis factor-α, and leptin regardless of the level of dietary selenium; supplemental selenium lowered plasma concentrations of plasminogen activator inhibitor-1 (P ≤ 0.05) and monocyte chemotactic protein-1 (P ≤ 0.05) in low-fat fed mice but not in high-fat fed mice. These results indicate that consumption of a high-fat diet abrogated the antimetastatic effects of selenium by increasing the expression of adipose-derived inflammatory cytokines.
authors: US Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202, USA lin.yan@ars.usda.gov.
authors: Lin
authors: L
authors: Yan
authors: US Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202, USA.
authors: Gerald F
authors: GF
authors: Combs
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001823:Body Composition / Q000187:drug effects; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000473:pathology*; D059305:Diet, High-Fat / Q000009:adverse effects*; D019587:Dietary Supplements; D020738:Leptin / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D016566:Organoselenium Compounds / Q000494:pharmacology*; D058258:Serpin E2 / Q000097:blood; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D016588:Anticarcinogenic Agents; D020738:Leptin; D016566:Organoselenium Compounds; D058258:Serpin E2; C511869:Serpine2 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C008493:methylselenic acid; D020780:Matrix Metalloproteinase 9