The ROS/JNK/ATF2 pathway mediates selenite-induced leukemia NB4 cell cycle arrest and apoptosis in vitro and in vivo.
The ROS/JNK/ATF2 pathway mediates selenite-induced leukemia NB4 cell cycle arrest and apoptosis in vitro and in vivo.
复制标题
DOI：
10.1038/cddis.2013.475
复制
发表时间：
2013-12-19
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
此前已经证明亚硒酸盐可以作为抗肿瘤药物并抑制癌细胞生长，尽管导致这种作用的机制尚不清楚。在这项研究中，我们已经证明了亚硒可以诱导NB4细胞的细胞周期停滞和凋亡。亚硒处理这些细胞也抑制了JNK/ATF2轴。进一步的实验证明，亚硒酸钠诱导的ROS的产生作为JNK/ATF2轴的上游发挥作用，导致细胞周期停滞和细胞凋亡。ATF2的失活导致该转录因子与细胞周期蛋白A、细胞周期蛋白D3和CDK4启动子的亲和力降低，导致NB4细胞停滞于G0/G1期。最后，体内实验证实了亚硒酸盐的抗肿瘤活性及其体外机制。综上所述，我们的结果表明，亚硒酸钠诱导的ROS在体内外通过抑制JNK/ATF2轴将NB4细胞阻滞在G0/G1期。
It has previously been shown that selenite can act as an antitumor agent and inhibit cancer cell growth, although the mechanism responsible for this effect is not well understood. In this study, we have shown that selenite can induce cell cycle arrest and apoptosis in NB4 cells. Selenite treatment of these cells also inhibited the JNK/ATF2 axis. Further experiments demonstrated that selenite-induced production of reactive oxygen species (ROS) worked as an upstream of the JNK/ATF2 axis, cell cycle arrest and apoptosis. Inactivation of ATF2 resulted in decreased affinity of this transcription factor for the promoters of cyclin A, cyclin D3 and CDK4, which led to the arrest of the NB4 cells in the G0/G1 phase. Finally, in vivo experiments confirmed the antitumor activity of selenite and the mechanisms that were described in vitro. Taken together, our results indicate that selenite-induced ROS arrest NB4 cells at G0/G1 phase through inhibiting the JNK/ATF2 axis in vitro and in vivo.
登录
查看更多内容
影响因子：
3.7
作者：
NAKAMURA, T;OKUYAMA, S;ODA, K
通讯作者：
ODA, K
影响因子：
4.1
作者：
Baan, Bart;van der Zon, Gerard C. M.;Ouwens, D. Margriet
通讯作者：
Ouwens, D. Margriet
影响因子：
3.1
作者：
Li, Zhu-shi;Shi, Ke-jian;Xu, Cai-min
通讯作者：
Xu, Cai-min
影响因子：
3.5
作者：
Park, Shin-Hyung;Kim, Jeong-Hwan;Choi, Yung Hyun
通讯作者：
Choi, Yung Hyun
影响因子：
4.7
作者：
Kristjansdottir, Katrin;Kim, Kyukwang;Singh, Rakesh K.
通讯作者：
Singh, Rakesh K.