Enantioselective Effects of o,p'-DDT on Cell Invasion and Adhesion of Breast Cancer Cells: Chirality in Cancer Development.

Abstract

The o,p'-dichlorodiphenyltrichloroethane (DDT) with a chiral center possesses enantioselective estrogenic activity, in which R-(-)-o,p'-DDT exerts a more potent estrogenic effect than S-(+)-o,p'-DDT. Although concern regarding DDT exposure and breast cancer has increased in recent decades, the mode of enantioselective action of o,p'-DDT in breast cancer development is still unknown. Herein, we conducted a systematic study of the effect of o,p'-DDT on stereoselective breast tumor cell progression in a widely used in vitro breast tumor cell model, MCF-7 cells. We demonstrated that R-(-)-o,p'-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-(-)-o,p'-DDT and human ER was stronger than that of S-(+)-o,p'-DDT. The enantioselective-induced decrease in cell-to-cell adhesion may involve the downregulation of adhesion-promoted genes (E-cadherin and β-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.

• Authors: Xiangming He, Xiaowu Dong, Dehong Zou, Yang Yu, Qunying Fang, Quan Zhang, Meirong Zhao
• Journal: Environmental science & technology (Environ Sci Technol) Vol. 49 Issue 16 Pg. 10028-37 (Aug 18 2015) ISSN: 1520-5851 [Electronic] United States
• PMID: 26225806 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• RNA, Messenger
• DDT
• o,p'-DDT
• Telomerase

Topics

• Biomarkers, Tumor (metabolism)
• Breast Neoplasms (genetics, pathology)
• Carcinogenesis (drug effects, pathology)
• Cell Adhesion (drug effects)
• DDT (chemistry, pharmacology)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• MCF-7 Cells
• Molecular Docking Simulation
• Neoplasm Invasiveness
• RNA, Messenger (genetics, metabolism)
• Real-Time Polymerase Chain Reaction
• Stereoisomerism
• Telomerase (genetics, metabolism)