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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.
AuthorsHuawei Zeng, Min Wu
JournalNutrition and cancer (Nutr Cancer) Vol. 67 Issue 5 Pg. 831-8 ( 2015) ISSN: 1532-7914 [Electronic] United States
PMID26011019 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Interleukin-6
  • Organoselenium Compounds
  • Tumor Necrosis Factor-alpha
  • methylselenic acid
  • Glutathione Peroxidase
  • Caspase 3
  • Selenium
Topics
  • Animals
  • Blotting, Western
  • Caspase 3 (metabolism)
  • Cell Proliferation (drug effects)
  • Colonic Neoplasms (blood, pathology, prevention & control)
  • Drug Evaluation, Preclinical
  • Glutathione Peroxidase (blood)
  • Heterografts
  • Interleukin-6 (blood)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Organoselenium Compounds (administration & dosage)
  • Selenium (metabolism)
  • Tumor Necrosis Factor-alpha (blood)

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