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

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.