TY - JOUR
T1 - Arsenic-induced S phase cell cycle lengthening is associated with ROS generation, p53 signaling and CDC25A expression
AU - Pozo-Molina, Glustein
AU - Ponciano-Gómez, Alberto
AU - Rivera-González, Guillermo Cipactl
AU - Hernández-Zavala, Araceli
AU - Garrido, Efraín
N1 - Publisher Copyright:
© 2015 Elsevier Ireland Ltd. All rights reserved.
PY - 2015/7/11
Y1 - 2015/7/11
N2 - 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.
AB - 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.
KW - Arsenite
KW - CDC25A
KW - ROS
KW - S phase lengthening
KW - SESN1
KW - p53
UR - http://www.scopus.com/inward/record.url?scp=84936854934&partnerID=8YFLogxK
U2 - 10.1016/j.cbi.2015.06.040
DO - 10.1016/j.cbi.2015.06.040
M3 - Artículo
SN - 0009-2797
VL - 238
SP - 170
EP - 179
JO - Chemico-Biological Interactions
JF - Chemico-Biological Interactions
ER -