title: Arsenic-induced S phase cell cycle lengthening is associated with ROS generation, p53 signaling and CDC25A expression.
abstract: Cellular response to arsenic is strongly dependent on p53 functional status. Primarily arresting the cell cycle in G1 or G2/M phases, arsenic treatment also induces an increase in the S-phase time in wild-type p53 cells. In contrast, cells with a non-functional p53 display only a subtle increase in the S phase, indicating arsenic differentially affects the cell cycle depending on p53 status. Importantly, it has been reported that arsenic induces reactive oxygen species (ROS), a process counteracted by p53. To evaluate the participation of p53 in the lengthening of the S phase and the connection between the transient cell cycle arrest and oxidative stress, we evaluated the cell response to arsenic in MCF-7 and H1299 cells, and analyzed p53's role as a transcription factor in regulating genes involved in ROS reduction and S phase transition. Herein, we discovered that arsenic induced an increase in the population of S phase cells that was dependent on the presence and transcriptional activity of p53. Furthermore, for the first time, we demonstrate that arsenic activates p53-dependent transcription of ROS detoxification genes, such as SESN1, and by an indirect mechanism involving ATF3, genes that could be responsible for the S phase cell cycle arrest, such as CDC25A.
authors.affiliation: Department of Genetics and Molecular Biology, CINVESTAV-IPN, Mexico City, Mexico; Facultad de Estudios Superiores Iztacala, UNAM, Tlalnepantla, Edo. de México, Mexico. Electronic address: jpozo@cinvestav.mx.
authors.forename: Glustein
authors.initials: G
authors.lastname: Pozo-Molina
authors.affiliation: Department of Genetics and Molecular Biology, CINVESTAV-IPN, Mexico City, Mexico. Electronic address: jponciano@cinvestav.mx.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ponciano-Gómez
authors.affiliation: Department of Molecular Cellular and Developmental Biology, Yale University, United States. Electronic address: guillermo.gonzalez@yale.edu.
authors.forename: Guillermo Cipactl
authors.initials: GC
authors.lastname: Rivera-González
authors.affiliation: Sección de Investigación y Posgrado, Escuela Superior de Medicina, IPN, Mexico City, Mexico. Electronic address: arhernanadez@ipn.mx.
authors.forename: Araceli
authors.initials: A
authors.lastname: Hernández-Zavala
authors.affiliation: Department of Genetics and Molecular Biology, CINVESTAV-IPN, Mexico City, Mexico. Electronic address: egarrido@cinvestav.mx.
authors.forename: Efraín
authors.initials: E
authors.lastname: Garrido
mesh_terms: D051700:Activating Transcription Factor 3 / Q000235:genetics / Q000378:metabolism; D018053:Arsenites / Q000633:toxicity*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D017670:Sodium Compounds / Q000633:toxicity*; D014158:Transcription, Genetic / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D020687:cdc25 Phosphatases / Q000235:genetics* / Q000378:metabolism*; D000084622:Sestrins
chemical_list: D051700:Activating Transcription Factor 3; D018053:Arsenites; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D017670:Sodium Compounds; D016159:Tumor Suppressor Protein p53; D020687:cdc25 Phosphatases; C490449:ATF3 protein, human; C117338:SESN1 protein, human; D000084622:Sestrins; C017947:sodium arsenite; C517004:CDC25A protein, human
keywords: Arsenite; CDC25A; ROS; S phase lengthening; SESN1; p53