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.

Methylseleninic acid promotes antitumour effects via nuclear FOXO3a translocation through Akt inhibition

“…These results are consistent with the fact that MSA is efficiently transformed into methylselenol which in turn can be methylated and excreted [74]. Therefore, MSA treatment presents superior in vivo antitumour efficacy with good tolerance results over other selenium derivates [8, 10, 71, 72]. …”

“…Indeed, dietary supplementation with MSA significantly inhibits xenograft tumour growth and reduces angiogenesis and spontaneous metastasis [8, 10, 71–73]. Importantly, supplementation with MSA does not affect neither the animal body weight nor the food consumption when compared with control diet animals, and histological alterations in organs are not observed, altogether indicating a good tolerance to the used dosage of MSA without adverse side effects [8, 71, 72]. Moreover, MSA supplementation results in less accumulation of selenium both in liver and primary tumour when compared with selenomethionine, while causes no increment in kidney selenium levels relative to controls [8, 10, 71].…”

Novel Methylselenoesters as Antiproliferative Agents

“…Consistently, the new CH 3 SeH precursors were also toxic for BEAS-2B and 184B5. Their toxicity, however, was in the same range as MSA, which has been broadly studied both in vitro and in vivo [ 7 , 47 ].…”

Colonic aberrant crypt formation accompanies an increase of opportunistic pathogenic bacteria in C57BL/6 mice fed a high-fat diet

“…Cell lysates were made by sonicating homogenized liver tissues at 4°C using a tissue lysis buffer (Cell Signaling Technologies, Inc., Danvers, MA, USA) as previously described [29]. The protein concentration was quantified by the Bradford dye-binding assay (Bio-Rad Laboratories, Hercules, CA, USA).…”