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PLoS One. 2014 Nov 11;9(11):e112700. doi: 10.1371/journal.pone.0112700. eCollection 2014.

p, p'-Dichlorodiphenyldichloroethylene induces colorectal adenocarcinoma cell proliferation through oxidative stress.

Author information

1
Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, China; MOE Key Lab of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, China.
2
Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, China.
3
Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, China; College of Life Science, Zhejiang Chinese Medical University, Hangzhou, China.
4
Research Center of Environmental Science, Zhejiang University of Technology, Hangzhou, China.
5
MOE Key Lab of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, China.

Abstract

p, p'-Dichlorodiphenyldichloroethylene (DDE), the major metabolite of Dichlorodiphenyltrichloroethane (DDT), is an organochlorine pollutant and associated with cancer progression. The present study investigated the possible effects of p,p'-DDE on colorectal cancer and the involved molecular mechanism. The results indicated that exposure to low concentrations of p,p'-DDE from 10(-10) to 10(-7) M for 96 h markedly enhanced proliferations of human colorectal adenocarcinoma cell lines. Moreover, p,p'-DDE exposure could activate Wnt/β-catenin and Hedgehog/Gli1 signaling cascades, and the expression level of c-Myc and cyclin D1 was significantly increased. Consistently, p,p'-DDE-induced cell proliferation along with upregulated c-Myc and cyclin D1 were impeded by β-catenin siRNA or Gli1 siRNA. In addition, p,p'-DDE was able to activate NADPH oxidase, generate reactive oxygen species (ROS) and reduce GSH content, superoxide dismutase (SOD) and calatase (CAT) activities. Treatment with antioxidants prevented p,p'-DDE-induced cell proliferation and signaling pathways of Wnt/β-catenin and Hedgehog/Gli1. These results indicated that p,p'-DDE promoted colorectal cancer cell proliferation through Wnt/β-catenin and Hedgehog/Gli1 signalings mediated by oxidative stress. The finding suggests an association between p,p'-DDE exposure and the risk of colorectal cancer progression.

PMID:
25386960
PMCID:
PMC4227882
DOI:
10.1371/journal.pone.0112700
[Indexed for MEDLINE]
Free PMC Article

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