Arsenic-induced S phase cell cycle lengthening is associated with ROS generation, p53 signaling and CDC25A expression.
Chem Biol Interact
; 238: 170-9, 2015 Aug 05.
Article
em En
| MEDLINE
| ID: mdl-26148435
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.
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Proteína Supressora de Tumor p53
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Espécies Reativas de Oxigênio
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Compostos de Sódio
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Arsenitos
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Fosfatases cdc25
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Pontos de Checagem da Fase S do Ciclo Celular
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article