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.

ACKNOWLEDGMENTS

The U.S. Department of Agriculture, Agricultural Research Service, Northern Plains Area, is an equal opportunity/affirmative action employer and all agency services are available without discrimination. The authors had no conflict of interest, and the work was directly funded by the U.S. Department of Agriculture, Agricultural Research Service. Mention of a trademark or proprietary product does not constitute a guarantee or warranty of the product by the U.S. Department of Agriculture and does not imply its approval to the exclusion of other products that may also be suitable. We are grateful to Drs. Matthew Picklo and Gerald Combs for their critical review of this manuscript. We also greatly appreciate Mary Briske-Anderson, Kay Keehr, Karen LoneFight, Lana DeMars, Craig Lacher, William Martin, LuAnn Johnson, and James Lindlauf for the technical support.

FUNDING

This work was directly funded by the US Department of Agriculture, Agricultural Research Service, CRIS project (5450-51000-045-00).