p, p'-Dichlorodiphenyldichloroethylene induces colorectal adenocarcinoma cell proliferation through oxidative stress.
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.
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.
Li
L
Song
Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, China.
Jianxin
J
Liu
Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan, China.
Xiaoting
X
Jin
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.
Zhuoyu
Z
Li
Research Center of Environmental Science, Zhejiang University of Technology, Hangzhou, China.
Meirong
M
Zhao
MOE Key Lab of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou, China.
Weiping
W
Liu
D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D003633:Dichlorodiphenyl Dichloroethylene / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D000071676:Zinc Finger Protein GLI1; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
C400551:GLI1 protein, human; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D051176:beta Catenin; D003633:Dichlorodiphenyl Dichloroethylene; D002374:Catalase; D013482:Superoxide Dismutase