title: The ROS/JNK/ATF2 pathway mediates selenite-induced leukemia NB4 cell cycle arrest and apoptosis in vitro and in vivo.
abstract: 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.
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: J J
authors.initials: JJ
authors.lastname: An
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: K J
authors.initials: KJ
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: F Y
authors.initials: FY
authors.lastname: Hua
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Y L
authors.initials: YL
authors.lastname: Ci
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: F
authors.initials: F
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: P
authors.initials: P
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: K Y
authors.initials: KY
authors.lastname: Hui
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: C M
authors.initials: CM
authors.lastname: Xu
mesh_terms: D051698:Activating Transcription Factor 2 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002460:Cell Line; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020887:Selenious Acid / Q000494:pharmacology*
chemical_list: C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D017382:Reactive Oxygen Species; D020887:Selenious Acid