Organophosphate ester tri-o-cresyl phosphate interacts with estrogen receptor α in MCF-7 breast cancer cells promoting cancer growth

Publication type:
Journal article
Metadata:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000525716200005&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.taap.2020.114977
eISSN
1096-0333
Externe Identifier
  • Clarivate Analytics Document Solution ID: LD0IG
  • PubMed Identifier: 32234386
ISSN
0041-008X
Zeitschrift
TOXICOLOGY AND APPLIED PHARMACOLOGY
Schlüsselwörter
  • TOCP
  • Organophosphate ester
  • Estrogen receptor
  • NGS
  • Endocrine disrupting chemical
Artikelnummer
ARTN 114977
Datum der Veröffentlichung
2020
Status
Published
Titel
Organophosphate ester tri-<i>o</i>-cresyl phosphate interacts with estrogen receptor α in MCF-7 breast cancer cells promoting cancer growth
Sub types
  • Article
Ausgabe der Zeitschrift
395

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
DOI
10.1016/j.taap.2020.114977
ISSN
0041-008X
Zeitschrift
Toxicology and Applied Pharmacology
Sprache
en
Artikelnummer
114977
Paginierung
114977 - 114977
Datum der Veröffentlichung
2020
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.taap.2020.114977
Datum der Datenerfassung
2020
Titel
Organophosphate ester tri-o-cresyl phosphate interacts with estrogen receptor α in MCF-7 breast cancer cells promoting cancer growth
Ausgabe der Zeitschrift
395

Data source: Crossref

Abstract
Plastic in the ocean degrades to microplastic, thereby enhancing the leaching of incorporated plasticizers due to the increased particle surface. The uptake of microplastic-derived plasticizers by marine animals and the subsequent entry in the food chain raises concerns for adverse health effects in human beings. Frequently used plasticizers as the organophosphate ester tri-o-cresyl phosphate (TOCP) are known to affect the male reproductive system. However, the overall endocrine potential of TOCP and the underlying molecular mechanisms remain elusive as yet. In this study, we investigated the molecular effects of TOCP on estrogen receptor α (ERα)-transfected HEK-ESR1 cells and the human breast cancer cell line MCF-7. Applying virtual screening and molecular docking, we identified TOCP as potent ligand of ERα in silico. Microscale thermophoresis confirmed the binding in vitro with similar intensity as the natural ligand 17-β-estradiol. To identify the molecular mechanisms of TOCP-mediated effects, we used next-generation sequencing to analyze the gene expression pattern of TOCP-treated MCF-7 cells. RNA-sequencing revealed 22 differently expressed genes associated with ESR1 as upstream regulator: CYP1A1, SLC7A11, RUNX2, DDIT4, STC2, KLHL24, CCNG2, CEACAM5, SLC7A2, MAP1B, SLC7A5, IGF1R, CD55, FOSL2, VEGFA, and HSPA13 were upregulated and PRKCD, CCNE1, CEBPA, SFPQ, TNFAIP2, KRT19 were downregulated. The affected genes promote tumor growth by increasing angiogenesis and nutritional supply, favor invasion and metastasis, and interfere with the cell cycle. Based on the gene expression pattern, we conclude TOCP to mediate endocrine effects on MCF-7 cells by interacting with ERα.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
Autoren
DOI
10.1016/j.taap.2020.114977
eISSN
1096-0333
Externe Identifier
  • PubMed Identifier: 32234386
Funding acknowledgements
  • Johannes Gutenberg University Mainz:
  • Deutsche Forschungsgemeinschaft: GRK 2015/2
Open access
false
ISSN
0041-008X
Zeitschrift
Toxicology and applied pharmacology
Schlüsselwörter
  • Humans
  • Breast Neoplasms
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neovascularization, Pathologic
  • Tritolyl Phosphates
  • Estrogen Receptor alpha
  • RNA
  • Plasticizers
  • Transfection
  • Cell Cycle
  • Gene Expression Regulation, Neoplastic
  • Models, Molecular
  • Female
  • Male
  • Endocrine Disruptors
  • HEK293 Cells
  • High-Throughput Nucleotide Sequencing
  • MCF-7 Cells
  • Molecular Docking Simulation
Sprache
eng
Medium
Print-Electronic
Online publication date
2020
Paginierung
114977
Datum der Veröffentlichung
2020
Status
Published
Datum der Datenerfassung
2020
Titel
Organophosphate ester tri-o-cresyl phosphate interacts with estrogen receptor α in MCF-7 breast cancer cells promoting cancer growth.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
395

Data source: Europe PubMed Central

Abstract
Plastic in the ocean degrades to microplastic, thereby enhancing the leaching of incorporated plasticizers due to the increased particle surface. The uptake of microplastic-derived plasticizers by marine animals and the subsequent entry in the food chain raises concerns for adverse health effects in human beings. Frequently used plasticizers as the organophosphate ester tri-o-cresyl phosphate (TOCP) are known to affect the male reproductive system. However, the overall endocrine potential of TOCP and the underlying molecular mechanisms remain elusive as yet. In this study, we investigated the molecular effects of TOCP on estrogen receptor α (ERα)-transfected HEK-ESR1 cells and the human breast cancer cell line MCF-7. Applying virtual screening and molecular docking, we identified TOCP as potent ligand of ERα in silico. Microscale thermophoresis confirmed the binding in vitro with similar intensity as the natural ligand 17-β-estradiol. To identify the molecular mechanisms of TOCP-mediated effects, we used next-generation sequencing to analyze the gene expression pattern of TOCP-treated MCF-7 cells. RNA-sequencing revealed 22 differently expressed genes associated with ESR1 as upstream regulator: CYP1A1, SLC7A11, RUNX2, DDIT4, STC2, KLHL24, CCNG2, CEACAM5, SLC7A2, MAP1B, SLC7A5, IGF1R, CD55, FOSL2, VEGFA, and HSPA13 were upregulated and PRKCD, CCNE1, CEBPA, SFPQ, TNFAIP2, KRT19 were downregulated. The affected genes promote tumor growth by increasing angiogenesis and nutritional supply, favor invasion and metastasis, and interfere with the cell cycle. Based on the gene expression pattern, we conclude TOCP to mediate endocrine effects on MCF-7 cells by interacting with ERα.
Date of acceptance
2020
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/32234386
DOI
10.1016/j.taap.2020.114977
eISSN
1096-0333
Zeitschrift
Toxicol Appl Pharmacol
Schlüsselwörter
  • Endocrine disrupting chemical
  • Estrogen receptor
  • NGS
  • Organophosphate ester
  • TOCP
  • Breast Neoplasms
  • Cell Cycle
  • Endocrine Disruptors
  • Estrogen Receptor alpha
  • Female
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • High-Throughput Nucleotide Sequencing
  • Humans
  • MCF-7 Cells
  • Male
  • Models, Molecular
  • Molecular Docking Simulation
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neovascularization, Pathologic
  • Plasticizers
  • RNA
  • Transfection
  • Tritolyl Phosphates
Sprache
eng
Country
United States
Paginierung
114977
PII
S0041-008X(20)30101-0
Datum der Veröffentlichung
2020
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2020
Titel
Organophosphate ester tri-o-cresyl phosphate interacts with estrogen receptor α in MCF-7 breast cancer cells promoting cancer growth.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
395

Data source: PubMed

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