Format

Send to

Choose Destination
Chem Biol Interact. 2015 Aug 5;238:170-9. doi: 10.1016/j.cbi.2015.06.040. Epub 2015 Jul 3.

Arsenic-induced S phase cell cycle lengthening is associated with ROS generation, p53 signaling and CDC25A expression.

Author information

1
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.
2
Department of Genetics and Molecular Biology, CINVESTAV-IPN, Mexico City, Mexico. Electronic address: jponciano@cinvestav.mx.
3
Department of Molecular Cellular and Developmental Biology, Yale University, United States. Electronic address: guillermo.gonzalez@yale.edu.
4
Sección de Investigación y Posgrado, Escuela Superior de Medicina, IPN, Mexico City, Mexico. Electronic address: arhernanadez@ipn.mx.
5
Department of Genetics and Molecular Biology, CINVESTAV-IPN, Mexico City, Mexico. Electronic address: egarrido@cinvestav.mx.

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.

KEYWORDS:

Arsenite; CDC25A; ROS; S phase lengthening; SESN1; p53

PMID:
26148435
DOI:
10.1016/j.cbi.2015.06.040
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center