Reactive oxygen species mediate Cr(VI)-induced S phase arrest through p53 in human colon cancer cells

Lijuan Sun; Xin Wang; Hua Yao; Wenqi Li; Young-Ok Son; Jia Luo; Jiankang Liu; Zhuo Zhang

doi:10.1615/JEnvironPatholToxicolOncol.v31.i2.20

Back

Reactive oxygen species mediate Cr(VI)-induced S phase arrest through p53 in human colon cancer cells

Journal article

Peer reviewed

Reactive oxygen species mediate Cr(VI)-induced S phase arrest through p53 in human colon cancer cells

Lijuan Sun, Xin Wang, Hua Yao, Wenqi Li, Young-Ok Son, Jia Luo, Jiankang Liu and Zhuo Zhang

Journal of environmental pathology, toxicology and oncology, Vol.31(2), pp.95-107

2012

DOI: 10.1615/JEnvironPatholToxicolOncol.v31.i2.20

PMID: 23216635

View Online

Abstract

Compounds that contain chromate (Cr(VI)) are well-known carcinogens that are present in both industrial settings and the environment. The mechanism of carcinogenesis associated with these compounds is not well understood. This study focused on Cr(VI)-induced cell cycle arrest in human colon adenocarcinoma DLD1 cells. Treatment of the cells with Cr(VI) at 2.5 µM caused a growth arrest at the S phase. An increase in Cr(VI) concentration enhanced the growth arrest. Superoxide dismutase did not alter the Cr(VI)-induced S phase arrest. Catalase inhibited S-cell growth, indicating that H(2)O(2) is an important mediator in Cr(VI)-induced S phase arrest. Electron spin resonance spin-trapping measurements showed that incubation of cells with Cr(VI) generated hydroxyl radical (·OH). Catalase inhibited ·OH generation, indicating that H(2)O(2) was generated from cells stimulated by Cr(VI) and that H(2)O(2) functioned as a precursor of ·OH radical generation. p53, an oxidative response transcription factor, was activated upon Cr(VI) stimulation. Inhibition of p53 by introducing small hairpin RNA decreased S phase arrest induced by Cr(VI). These results support the following conclusions: (1) reactive oxygen species (ROS) are generated in Cr(VI)-stimulated DLD1 cells; (2) among the ROS generated, H(2)O(2) played a major role in causing S phase arrest in DLD1 cells; and (3) ROS mediated S phase arrest through a p53-dependent pathway.

Adenocarcinoma - metabolism

Adenocarcinoma - pathology

Catalase - pharmacology

Cell Line, Tumor

Chromates - pharmacology

Colonic Neoplasms - metabolism

Colonic Neoplasms - pathology

Electron Spin Resonance Spectroscopy

Humans

Hydrogen Peroxide - metabolism

Hydroxides - metabolism

Reactive Oxygen Species - metabolism

RNA, Small Interfering - pharmacology

S Phase - drug effects

S Phase - physiology

Signal Transduction - drug effects

Signal Transduction - physiology

Superoxide Dismutase - pharmacology

Tumor Suppressor Protein p53 - antagonists & inhibitors

Tumor Suppressor Protein p53 - drug effects

Tumor Suppressor Protein p53 - metabolism

Details

Title: Subtitle: Reactive oxygen species mediate Cr(VI)-induced S phase arrest through p53 in human colon cancer cells
Creators: Lijuan Sun - University of Kentucky
Xin Wang - University of Kentucky
Hua Yao - Zhejiang University
Wenqi Li - University of Kentucky
Young-Ok Son
Jia Luo - University of Kentucky
Jiankang Liu - Xi'an Jiaotong University
Zhuo Zhang - University of Kentucky
Resource Type: Journal article
Publication Details: Journal of environmental pathology, toxicology and oncology, Vol.31(2), pp.95-107
DOI: 10.1615/JEnvironPatholToxicolOncol.v31.i2.20
PMID: 23216635
ISSN: 0731-8898
eISSN: 2162-6537
Grant note: R01ES018883 / NIEHS NIH HHS
Language: English
Date published: 2012
Academic Unit: Pathology
Record Identifier: 9984201250802771

Metrics

12 Record Views

15 Times Cited - Web of Science