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Issue 5, 2015
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p,p′-Dichlorodiphenyltrichloroethane inhibits the apoptosis of colorectal adenocarcinoma DLD1 cells through PI3K/AKT and Hedgehog/Gli1 signaling pathways

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Abstract

Dichlorodiphenyltrichloroethane (DDT) is a ubiquitous organochlorine pollutant in the environment and has been associated with colorectal cancer development. The present study investigated the possible effects of p,p′-DDT on the apoptosis of colorectal adenocarcinoma cells and the relevant molecular mechanism. The results indicated that exposure to low concentrations of p,p′-DDT (10−10, 10−9 and 10−8 M) for 96 h markedly inhibited the apoptosis of human colorectal adenocarcinoma DLD1 cells induced by 5-FU. Moreover, p,p′-DDT exposure led to upregulation of Bcl-2 along with downregulation of Bax and procaspase-3 in both DLD1 cells and tumor tissue of a mouse xenograft model. We also found that activated caspase-3 activity was decreased after p,p′-DDT treatment. The addition of estrogen receptor (ER) inhibitor, ICI 182780, had no significant effect on the action of p,p′-DDT. In addition, p,p′-DDT exposure could activate PI3K/AKT and Hedgehog/Gli1 signaling cascades. Treatment with the PI3K inhibitor LY294003 or the Hedgehog/Gli1 inhibitor GANT61 prevented p,p′-DDT-induced signaling pathways of PI3K/AKT and Hedgehog/Gli1, respectively. Consistently, LY294003 or GANT61 attenuated the ability of p,p′-DDT to suppress 5-FU-induced apoptosis in DLD1 cells. Taken together, our results demonstrated that p,p′-DDT inhibited the apoptosis of human colorectal adenocarcinoma DLD1 cells by activating PI3K/AKT and Hedgehog/Gli1 signaling pathways.

Graphical abstract: p,p′-Dichlorodiphenyltrichloroethane inhibits the apoptosis of colorectal adenocarcinoma DLD1 cells through PI3K/AKT and Hedgehog/Gli1 signaling pathways

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Publication details

The article was received on 07 Jan 2015, accepted on 27 May 2015 and first published on 02 Jun 2015


Article type: Paper
DOI: 10.1039/C5TX00006H
Toxicol. Res., 2015,4, 1214-1224

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    p,p′-Dichlorodiphenyltrichloroethane inhibits the apoptosis of colorectal adenocarcinoma DLD1 cells through PI3K/AKT and Hedgehog/Gli1 signaling pathways

    L. Song, M. Zhao, J. Liu, Z. Li, H. Xiao and W. Liu, Toxicol. Res., 2015, 4, 1214
    DOI: 10.1039/C5TX00006H

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