Indeno[1,2,3-cd]pyrene and picene mediate actions via estrogen receptor α signaling pathway in in vitro cell systems, altering gene expression

Publication type:
Journal article
Metadata:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000529799700003&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.taap.2020.114995
eISSN
1096-0333
Externe Identifier
  • Clarivate Analytics Document Solution ID: LI9ME
  • PubMed Identifier: 32251684
ISSN
0041-008X
Zeitschrift
TOXICOLOGY AND APPLIED PHARMACOLOGY
Schlüsselwörter
  • PAH
  • Indeno[1,2,3-cd]pyrene
  • Picene
  • Estrogen receptor
  • Microplastic
Artikelnummer
ARTN 114995
Datum der Veröffentlichung
2020
Status
Published
Titel
Indeno[1,2,3-<i>cd</i>]pyrene and picene mediate actions <i>via</i> estrogen receptor α signaling pathway in <i>in vitro</i> cell systems, altering gene expression
Sub types
  • Article
Ausgabe der Zeitschrift
396

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
DOI
10.1016/j.taap.2020.114995
ISSN
0041-008X
Zeitschrift
Toxicology and Applied Pharmacology
Sprache
en
Artikelnummer
114995
Paginierung
114995 - 114995
Datum der Veröffentlichung
2020
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.taap.2020.114995
Datum der Datenerfassung
2021
Titel
Indeno[1,2,3-cd]pyrene and picene mediate actions via estrogen receptor α signaling pathway in in vitro cell systems, altering gene expression
Ausgabe der Zeitschrift
396

Data source: Crossref

Abstract
Currently, the environmental impact of ubiquitous plastic debris triggered quite some public attention. However, the global impact of microplastic on human health is by and large either unknown or neglected. By looking at the underlying biochemical mechanisms leading to the global health threat microplastic was discovered to carry persistent organic pollutants, such as polycyclic aromatic hydrocarbons (PAH), to marine life. The effect of microplastic-ingestion in the human body remains unfortunately somewhat elusive as of yet. For this reason, we screened for compounds binding to the human estrogen receptor α (ERα) and identified the PAH compounds indeno[1,2,3-cd]pyrene (Indpy) and picene (Pice) with a high binding affinity. We applied next generation sequencing to analyze the differentially expressed genes in MCF-7 cells after treatment with Indpy and Pice. We found 8 upregulated genes: ABCC5, CCNG2, CYP1A1, DDIT4, IER3, RUNX2, STC2, and SLC7A5 and 14 downregulated genes: ADORA1, CEBPB, CELSR2, CTSD, CXCL12, KRT19, PGR, PKIB, RARA, RET, SEMA3B, SIAH2, TFAP2C, and XBP1 induced by both ligands and associated with ESR1-regulation. The altered gene expression may influence cell proliferation and metastasis, favoring cancer development with a poor response to therapy. In addition, we confirmed the binding of Indpy and Pice to ERα using molecular docking and microscale thermophoresis. ERα activation was measured with ESR1-overexpressing HEK293 (HEK-ESR1) cells and confirmed for Indpy. In conclusion, we showed an ESR1-mediated influence of the PAH compounds Indpy and Pice on the gene expression pattern of MCF-7 cells, possibly also promoting breast cancer development in patients.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Mainz, Germany.
Autoren
DOI
10.1016/j.taap.2020.114995
eISSN
1096-0333
Externe Identifier
  • PubMed Identifier: 32251684
Funding acknowledgements
  • Deutsche Forschungsgemeinschaft: GRK 2015/2
  • Johannes Gutenberg University Mainz:
Open access
false
ISSN
0041-008X
Zeitschrift
Toxicology and applied pharmacology
Schlüsselwörter
  • Humans
  • Chrysenes
  • Pyrenes
  • Estrogen Receptor alpha
  • Signal Transduction
  • Gene Expression
  • Gene Expression Regulation
  • Real-Time Polymerase Chain Reaction
  • MCF-7 Cells
  • Molecular Docking Simulation
Sprache
eng
Medium
Print-Electronic
Online publication date
2020
Paginierung
114995
Datum der Veröffentlichung
2020
Status
Published
Datum der Datenerfassung
2020
Titel
Indeno[1,2,3-cd]pyrene and picene mediate actions via estrogen receptor α signaling pathway in in vitro cell systems, altering gene expression.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
Ausgabe der Zeitschrift
396

Data source: Europe PubMed Central

Abstract
Currently, the environmental impact of ubiquitous plastic debris triggered quite some public attention. However, the global impact of microplastic on human health is by and large either unknown or neglected. By looking at the underlying biochemical mechanisms leading to the global health threat microplastic was discovered to carry persistent organic pollutants, such as polycyclic aromatic hydrocarbons (PAH), to marine life. The effect of microplastic-ingestion in the human body remains unfortunately somewhat elusive as of yet. For this reason, we screened for compounds binding to the human estrogen receptor α (ERα) and identified the PAH compounds indeno[1,2,3-cd]pyrene (Indpy) and picene (Pice) with a high binding affinity. We applied next generation sequencing to analyze the differentially expressed genes in MCF-7 cells after treatment with Indpy and Pice. We found 8 upregulated genes: ABCC5, CCNG2, CYP1A1, DDIT4, IER3, RUNX2, STC2, and SLC7A5 and 14 downregulated genes: ADORA1, CEBPB, CELSR2, CTSD, CXCL12, KRT19, PGR, PKIB, RARA, RET, SEMA3B, SIAH2, TFAP2C, and XBP1 induced by both ligands and associated with ESR1-regulation. The altered gene expression may influence cell proliferation and metastasis, favoring cancer development with a poor response to therapy. In addition, we confirmed the binding of Indpy and Pice to ERα using molecular docking and microscale thermophoresis. ERα activation was measured with ESR1-overexpressing HEK293 (HEK-ESR1) cells and confirmed for Indpy. In conclusion, we showed an ESR1-mediated influence of the PAH compounds Indpy and Pice on the gene expression pattern of MCF-7 cells, possibly also promoting breast cancer development in patients.
Date of acceptance
2020
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/32251684
DOI
10.1016/j.taap.2020.114995
eISSN
1096-0333
Zeitschrift
Toxicol Appl Pharmacol
Schlüsselwörter
  • Estrogen receptor
  • Indeno[1,2,3-cd]pyrene
  • Microplastic
  • PAH
  • Picene
  • Chrysenes
  • Estrogen Receptor alpha
  • Gene Expression
  • Gene Expression Regulation
  • Humans
  • MCF-7 Cells
  • Molecular Docking Simulation
  • Pyrenes
  • Real-Time Polymerase Chain Reaction
  • Signal Transduction
Sprache
eng
Country
United States
Paginierung
114995
PII
S0041-008X(20)30119-8
Datum der Veröffentlichung
2020
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2020
Titel
Indeno[1,2,3-cd]pyrene and picene mediate actions via estrogen receptor α signaling pathway in in vitro cell systems, altering gene expression.
Sub types
  • Journal Article
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
396

Data source: PubMed

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