The organochlorine p,p'-dichlorodiphenyltrichloroethane induces colorectal cancer growth through Wnt/β-catenin signaling

Li Song, Junyu Zhao, Xiaoting Jin, Zhuoyu Li (Lead / Corresponding author), Ian P. Newton, Weiping Liu, Hong Xiao, Meirang Zhao (Lead / Corresponding author)

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    16 Citations (Scopus)

    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 to 10M for 96h. Exposure to p,p'-DDT from 10 to 10M led to upregulation of phospho-GSK3ß (Ser9), ß-catenin, c-Myc and cyclin D1 in DLD1 cells. RNA interference of ß-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/ß-catenin signaling and DLD1 cell proliferation by p,p'-DDT. Moreover, in a mouse xenograft model, 5nmol/kg p,p'-DDT resulted in increased tumor size, oxidative stress and Wnt/ß-catenin signaling. These results indicated that low concentrations of p,p'-DDT promoted colorectal cancer growth through Wnt/ß-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.
    Original languageEnglish
    Pages (from-to)284-291
    Number of pages8
    JournalToxicology Letters
    Volume229
    Issue number1
    Early online date23 Jun 2014
    DOIs
    Publication statusPublished - 17 Aug 2014

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