title: The organochlorine p,p'-dichlorodiphenyltrichloroethane induces colorectal cancer growth through Wnt/β-catenin signaling.
abstract: Dichlorodiphenyltrichloroethane (DDT), an organochlorine pollutant, is associated with several types of cancer. However, the relationship between DDT and colorectal cancer is uncertain. In this study, the impact of p,p'-DDT on colorectal cancer growth was evaluated using both in vitro and in vivo models. Our results indicated that the proliferation of human colorectal adenocarcinoma DLD1 cells was significantly promoted after exposed to low concentrations of p,p'-DDT ranging from 10(-12) to 10(-7) M for 96 h. Exposure to p,p'-DDT from 10(-10) to 10(-8) M led to upregulation of phospho-GSK3β (Ser9), β-catenin, c-Myc and cyclin D1 in DLD1 cells. RNA interference of β-catenin inhibited the proliferation of DLD1 cells stimulated by p,p'-DDT. Inhibiting of estrogen receptors (ERs) had no significant effect on the action of p,p'-DDT. Treatment with p,p'-DDT induced production of intracellular reactive oxygen species (ROS) and inhibited superoxide dismutase (SOD) activity in DLD1 cells. Treatment with N-acetyl-L-cysteine (NAC), a ROS inhibitor, suppressed the induction of Wnt/β-catenin signaling and DLD1 cell proliferation by p,p'-DDT. Moreover, in a mouse xenograft model, 5 nmol/kg p,p'-DDT resulted in increased tumor size, oxidative stress and Wnt/β-catenin signaling. These results indicated that low concentrations of p,p'-DDT promoted colorectal cancer growth through Wnt/β-catenin signaling, which was mediated by oxidative stress. The finding suggests an association between low concentrations of p,p'-DDT exposure and colorectal cancer progression.
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China; MOE Key Lab of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.
authors: Li
authors: L
authors: Song
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors: Junyu
authors: J
authors: Zhao
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors: Xiaoting
authors: X
authors: Jin
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China; College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China. Electronic address: lzy@sxu.edu.cn.
authors: Zhuoyu
authors: Z
authors: Li
authors: Division of Cell & Developmental Biology, University of Dundee, Dow Street, Dundee DD1 5EH, UK.
authors: Ian P
authors: IP
authors: Newton
authors: MOE Key Lab of Environmental Remediation and Ecosystem Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058, China.
authors: Weiping
authors: W
authors: Liu
authors: Department of Parthology, The First Affiliated Hospital, Shanxi Medical University, Taiyuan 030001, China.
authors: Hong
authors: H
authors: Xiao
authors: Research Center of Environmental Science, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address: zhaomr@zjut.edu.cn.
authors: Meirong
authors: M
authors: Zhao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000139:chemically induced* / Q000473:pathology*; D003634:DDT / Q000633:toxicity*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007150:Immunohistochemistry; D007306:Insecticides / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D034622:RNA Interference; D017382:Reactive Oxygen Species / Q000378:metabolism; D011960:Receptors, Estrogen / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology*
chemical_list: D007306:Insecticides; D017382:Reactive Oxygen Species; D011960:Receptors, Estrogen; D051153:Wnt Proteins; D051176:beta Catenin; D003634:DDT; D013482:Superoxide Dismutase; D005978:Glutathione
keywords: Colorectal cancer; Dichlorodiphenyltrichloroethane; Organochlorine pesticides; Reactive oxygen species; Wnt/β-catenin signaling