Mounting evidence reveals that selenium possesses chemotherapeutic potential against cancer cells. However, the molecular mechanisms underlying the anti-cancer effect of selenium remain elusive. In this study, with the aim to explore the detailed mechanisms how selenite induces apoptosis in colorectal cancer cells, we investigated the role of AKT/β-catenin signaling, a critical regulator of cell proliferation, survival and tumorigenesis, in selenite-induced apoptosis of colorectal cancer cells and xenograft tumors. We showed that selenite exerted a remarkable inhibitory effect on activation of AKT, leading to suppression of β-catenin activity and expression of its targets: cyclin D1 and survivin. Further experiments by transient expression of AKT and β-catenin revealed that inhibition of AKT/β-catenin was closely correlated with selenite-triggered apoptosis. Importantly, MnTMPyP pretreatment implied reactive oxygen species (ROS) was a crucial upstream signal for selenite-triggered inhibition of AKT/β-catenin. Overall, these observations demonstrate that selenite could induce apoptosis through ROS-dependent inhibition of AKT/β-catenin signaling in colorectal cancer cells in vitro and in vivo, and our findings yield novel insights into elucidating the mechanisms involved in the anti-cancer effect of selenium.
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