Abstract
Methylselenol is hypothesized to be a critical selenium (Se) metabolite for anticancer activity. In this study, submicromolar methylselenol was generated by incubating methionase with seleno-L methionine, and both colon-cancer-derived HCT-116 cells and noncancerous colon NCM460 cells were exposed to methylselenol. Methylselenol exposure inhibited cell growth and led to an increase in the G1 and G2 fractions with a concomitant drop in the S-phase, and an induction of apoptosis in HCT116, but to a much lesser extent in NCM460 colon cells. The examination of mitogen-activated protein kinase (MAPK) and c-Myc signaling status revealed that methylselenol inhibited the phosphorylation of extracellular-regulated kinase1/2 (ERK1/2) and p38 MAPK, and the expression of c-Myc in HCT116 cells, but also to a lesser extent in NCM460 cells. The other important finding is that methylselenol inhibits Src phosphorylation in HCT116 cells. In sharp contrast, methylselenol up-regulated the phosphorylation of both Src and FAK survival signals in NCM460 cells. In addition to the above findings on human colon cells, we also found that methylselenol inhibited the growth of MC-26 colon cancer xenografts in Balb/c mice. Taken together, methylselenol's stronger potential of inhibiting colon cancer cell proliferation, may be a critical mechanism by which selenium exerts its anticancer activity. Supported by USDA/ARS
Published Version
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