Enantioselective Effects of o,p鈥?DDT on Cell Invasion and Adhesion of Breast Cancer Cells: Chirality in Cancer Development

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• 作者：Xiangming He ; Xiaowu Dong ; Dehong Zou ; Yang Yu ; Qunying Fang ; Quan Zhang ; Meirong Zhao
• 刊名：Environmental Science & Technology
• 出版年：2015
• 出版时间：August 18, 2015
• 年：2015
• 卷：49
• 期：16
• 页码：10028-10037
• 全文大小：500K
• ISSN：1520-5851

文摘

The o,p鈥?dichlorodiphenyltrichloroethane (DDT) with a chiral center possesses enantioselective estrogenic activity, in which R-(鈭?-o,p鈥?DDT exerts a more potent estrogenic effect than S-(+)-o,p鈥?DDT. Although concern regarding DDT exposure and breast cancer has increased in recent decades, the mode of enantioselective action of o,p鈥?DDT in breast cancer development is still unknown. Herein, we conducted a systematic study of the effect of o,p鈥?DDT on stereoselective breast tumor cell progression in a widely used in vitro breast tumor cell model, MCF-7 cells. We demonstrated that R-(鈭?-o,p鈥?DDT promoted more cancer cell invasion mediated by the human estrogen receptor (ER) by inducing invasion-promoted genes (matrix metalloproteinase-2 and -9 and human telomerase reverse transcriptase) and inhibiting invasion-inhibited genes (tissue inhibitor of metalloproteinase-1 and -4). Molecular docking verified that the binding affinity between R-(鈭?-o,p鈥?DDT and human ER was stronger than that of S-(+)-o,p鈥?DDT. The enantioselective-induced decrease in cell-to-cell adhesion may involve the downregulation of adhesion-promoted genes (E-cadherin and 尾-catenin). For the first time, these results reveal that estrogenic-like chiral compounds are of significant concern in the progression of human cancers and that human health risk assessment of chiral chemicals should consider enantioselectivity.