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Methylselenol, a selenium metabolite, inhibits colon cancer cell growth and cancer xenografts in C57BL/6 mice (374.2)
Author(s) -
Zeng Huawei
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.374.2
Subject(s) - colorectal cancer , apoptosis , in vivo , tumor necrosis factor alpha , cancer , chemistry , metabolite , cell growth , cancer cell , glutathione peroxidase , cancer research , necrosis , medicine , endocrinology , glutathione , biology , enzyme , biochemistry , microbiology and biotechnology
Data indicate that methylselenol is a critical selenium (Se) metabolite for anticancer activity in vivo but its role in colon cancer prevention remains to be characterized. This study tested the hypothesis that methylselenol inhibits the growth of colon cancer cells and tumors. We found that submicromolar methylselenol exposure induced apoptosis and inhibited cell growth in cancerous colon HCT116 cells through a blockade of extracellular‐regulated kinase1/2 (ERK1/2) pathway, but to a much lesser extent in noncancerous NCM460 colon cells. Consistent with these in vitro observations, a daily single oral dose (0, 1 or 3 mg Se/kg body weight) of methylseleninic acid (MSeA), a methylselenol precursor, for 5 weeks inhibited colon tumor volume and tumor burden (weight) up to 61% when compared with control group, and this inhibition was associated with a reduction of plasma tumor necrosis factor (TNFα) level but high blood glutathione peroxidase (GPx) activities in C57BL/6 mice supplemented with MSeA. Furthermore, 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, cancer cell specific inhibition, high blood GPx activities, caspase‐3 activities in tumor tissue and a reduction of plasma TNFα may be part of the underlying molecular basis for Se’s protective effect against colon tumor growth.