title: 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.affiliation: †Zhejiang Cancer Hospital, Hangzhou 310022, China.|§College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Xiangming
authors.initials: X
authors.lastname: He
authors.affiliation: ‡College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Dong
authors.affiliation: †Zhejiang Cancer Hospital, Hangzhou 310022, China.
authors.forename: Dehong
authors.initials: D
authors.lastname: Zou
authors.affiliation: †Zhejiang Cancer Hospital, Hangzhou 310022, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: †Zhejiang Cancer Hospital, Hangzhou 310022, China.
authors.forename: Qunying
authors.initials: Q
authors.lastname: Fang
authors.affiliation: §College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: §College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Meirong
authors.initials: M
authors.lastname: Zhao
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D063646:Carcinogenesis / Q000187:drug effects / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D003634:DDT / Q000737:chemistry* / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013237:Stereoisomerism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D003634:DDT; C016340:o,p'-DDT; D019098:Telomerase