Selenite induces apoptosis in colorectal cancer cells via AKT-mediated inhibition of β-catenin survival axis
Selenite induces apoptosis in colorectal cancer cells via AKT-mediated inhibition of β-catenin survival axis
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DOI：
10.1016/j.canlet.2011.10.014
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发表时间：
2012-02-01
期刊：
影响因子：
9.7
通讯作者：
Xu, Caimin
中科院分区：
文献类型：
--
作者：
Luo, Hui;Yang, Yang;Xu, Caimin
越来越多的证据表明，硒具有抗癌细胞的化疗潜力。然而，硒的抗癌作用的分子机制仍然难以捉摸。在这项研究中，为了探索亚硒酸盐诱导结直肠癌细胞凋亡的详细机制，我们研究了AKT/β-catenin信号转导（细胞增殖、存活和肿瘤发生的关键调节因子）在亚硒酸盐诱导结直肠癌细胞和异种移植肿瘤凋亡中的作用。我们发现，亚硒酸盐对Ala的激活产生了显着的抑制作用，导致抑制β-连环蛋白的活性及其靶点：细胞周期蛋白D1和生存素的表达。通过瞬时表达AKT和β-catenin的进一步实验显示，AKT/β-catenin的抑制与亚硒酸盐触发的细胞凋亡密切相关。重要的是。MnTMPyP预处理暗示活性氧（ROS）是亚硒酸盐触发的AKT/β-catenin抑制的关键上游信号。总体而言，这些观察结果表明，亚硒酸盐可以诱导凋亡，通过ROS依赖性抑制AKT/β-catenin信号在大肠癌细胞在体外和体内，我们的研究结果产生新的见解阐明参与硒的抗癌作用的机制。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
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/beta-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 Ala, leading to suppression of beta-catenin activity and expression of its targets: cyclin D1 and survivin. Further experiments by transient expression of AKT and beta-catenin revealed that inhibition of AKT/beta-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/beta-catenin. Overall, these observations demonstrate that selenite could induce apoptosis through ROS-dependent inhibition of AKT/beta-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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.