|WU, MIN - University Of North Dakota|
Submitted to: Nutrition and Cancer
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/9/2015
Publication Date: 5/26/2015
Publication URL: http://handle.nal.usda.gov/10113/61058
Citation: Zeng, H., Wu, M. 2015. The inhibitory efficacy of methylseleninic acid against colon cancer xenografts in C57BL/6 mice. Nutrition and Cancer. 67(5):831-838.
Interpretive Summary: Epidemiological evidence indicates that selenium (Se) status is inversely associated with cancer risk, and results from several intervention studies show that high Se intakes effectively reduce colon cancer risk. It has been documented that methylseleninic acid (MSeA), a methylselenol precursor, is a superior choice of Se for cancer chemoprevention over other Se compounds. In viewing of the strong association between immunity / primary cancer types and Se anticancer action, it will be of interest to characterize the effect of MSeA on inhibitory efficacy of MSeA against other cancer types. In our present study, the oral dosing MSeA supplementation (1 or 3 mg MSeA/kg body wt) did not change body weight growth curve, body composition and daily food intake. However, the MSeA supplementation at this level significantly inhibited colon cancer growth in a mouse model. This observation demonstrated that MSeA has a strong potential against colon cancer. The information will be useful for scientists and health-care professionals who are interested in using Se as a nutrient and cancer prevention.
Technical Abstract: Data indicate that methylselenol is a critical selenium (Se) metabolite for anticancer activity in vivo. We tested the hypoththesis 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 a single oral dose (0, 1 or 3 mg/kg body wt) regimen every 48 h for two weeks before the subcutaneous inoculation of cancer cells, and then daily oral dose starting on the day of subcutaneous inoculation of cancer cells until the end of the study. Oral MSeA supplementation increased Se content of liver, kidney, muscle and plasma and elevated blood glutathione peroxidase (GPx) activities. MSeA supplementation did not change lean/fat body composition, food consumption, plasma leptin level and body weight gain. MSeA (3 mg/kg body wt) inhibited tumor volume and tumor burden (weight) up to 61% when compared to the control group, and this inhibition was associated with a reduction of plasma tumor necrosis factor (TNF alpha'level but elevated blood GPx activities. In addition, we also found that MSeA (1 mg/kg body wt) increased the activation of caspase-3, a major apoptotic enzyme, in tumor tissues. Taken together, the MSeA oral dosing regimen inhibited colon tumor growth, which is associated with high blood GPx activities, caspase-3 activities in tumor tissue and a reduction of plasma TNF alpha level in an immune-competent C57BL/6 mouse model.