Methylselenol, a selenium metabolite, inhibits colon cancer cell growth in vitro and in vivo

Abstract

Methylselenol is hypothesized to be a critical selenium (Se) metabolite for certain anticancer activities 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 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 cancerous colon HCT116 cells, but to a much lesser extent in noncancerous NCM460 colon cells. Furthermore, in agreement with the fact that blockade of extracellular‐regulated kinase1/2 (ERK1/2) and p38 mitogen activated protein kinase (p38 MAPK) pathways suppresses the growth of colon tumors, we demonstrated that methylselenol inhibited ERK1/2 and p38 MAPK in cancerous colon HCT116 cells but also to a lesser extent in NCM460 cells. Consistent with these in vitro observations, a daily single oral dose (1 to 3 mg Se/kg body weight) of methylseleninic acid, a methylselenol precursor, for 5 weeks inhibits the growth of colon cancer xenografts in a C57/BL mouse model. Taken together, methylselenol's strong potential of inhibiting colon cancer cell proliferation, may be an important mechanism by which Se exerts its anticancer activity in colon cancer prevention.