title: Selenite induces apoptosis in colorectal cancer cells via AKT-mediated inhibition of β-catenin survival axis.
abstract: 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.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Luo
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Fang
authors.initials: F
authors.lastname: Huang
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.forename: Kejian
authors.initials: K
authors.lastname: Shi
authors.forename: Caimin
authors.initials: C
authors.lastname: Xu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045325:HCT116 Cells; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018038:Sodium Selenite / Q000494:pharmacology*; D016019:Survival Analysis; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D051176:beta Catenin; D051057:Proto-Oncogene Proteins c-akt; D018038:Sodium Selenite