title: The Inhibitory Efficacy of Methylseleninic Acid Against Colon Cancer Xenografts in C57BL/6 Mice.
abstract: Data indicate that methylselenol is a critical selenium (Se) metabolite for anticancer activity in vivo. We tested the hypothesis that oral dosing methylseleninic acid (MSeA), a methylselenol precursor, inhibits the growth of colon cancer xenografts in C57BL/6 mice fed a Se adequate diet. In this study, MSeA supplementation was given by an oral dose (0, 1, or 3 mg/kg body weight) regimen. MSeA increased Se content of liver, kidney, muscle, stomach (w/intestine) and plasma, and elevated blood glutathione peroxidase (GPx) activities. However, MSeA did not change lean/fat body composition, food consumption, levels of plasma leptin/adiponectin, and body weight gain. MSeA (3 mg/kg body weight) inhibited tumor growth up to 61% when compared to the control group, and this inhibition was associated with a reduction of plasma tumor necrosis factor (TNFα)/interleukin 6 (IL6) level but elevated blood GPx activities. In addition, MSeA (1 mg/kg body weight) increased the activation of caspase-3, a major apoptotic enzyme, in tumor tissues. Taken together, our MSeA oral dosing regimen was at safe levels; and high blood GPx activities, caspase-3 activities in tumor tissue and a reduction of plasma TNFα/IL6 level, play critical roles in inhibiting colon tumor growth in an immune-competent C57BL/6 mouse model.
authors.affiliation: a Grand Forks Human Nutrition Research Center, Agricultural Research Service, United States Department of Agriculture , Grand Forks , North Dakota , USA.
authors.forename: Huawei
authors.initials: H
authors.lastname: Zeng
authors.forename: Min
authors.initials: M
authors.lastname: Wu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D004353:Drug Evaluation, Preclinical; D005979:Glutathione Peroxidase / Q000097:blood; D064593:Heterografts; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D016566:Organoselenium Compounds / Q000008:administration & dosage*; D012643:Selenium / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D016566:Organoselenium Compounds; D014409:Tumor Necrosis Factor-alpha; C008493:methylselenic acid; D005979:Glutathione Peroxidase; D053148:Caspase 3; D012643:Selenium