Impact of Plastic-Related Compounds on P-Glycoprotein and Breast Cancer Resistance Protein In Vitro
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Matteo Rosellini
- Petri Turunen
- Thomas Efferth
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000959843200001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.3390/molecules28062710
- eISSN
- 1420-3049
- Externe Identifier
- Clarivate Analytics Document Solution ID: C1UE1
- PubMed Identifier: 36985682
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- MOLECULES
- Schlüsselwörter
- plastic
- microplastic
- cytotoxicity
- uptake
- live cell imaging
- microscopy
- Artikelnummer
- ARTN 2710
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Titel
- Impact of Plastic-Related Compounds on P-Glycoprotein and Breast Cancer Resistance Protein In Vitro
- Sub types
- Article
- Ausgabe der Zeitschrift
- 28
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Abstract
- <jats:p>Plastic in oceans degrades to microplastics and nanoplastics, causing various problems for marine fauna and flora. Recently, microplastic has been detected in blood, breast milk and placenta, underlining their ability to enter the human body with still unknown effects. In addition, plastic contains other compounds such as plasticizers, antioxidants or lubricants, whose impact on human health is also elusive. On the cellular level, two transporters involved in cell protection and detoxification of xenobiotic compounds are the ABC-transporters P-glycoprotein (P-gp, MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2). Despite the great importance of these proteins to maintain the correct cellular balance, their interaction with plastic and related products is evasive. In this study, the possible interaction between different plastic-related compounds and these two transporters was investigated. Applying virtual compound screening and molecular docking of more than 1000 commercially available plastic compounds, we identified candidates most probably interacting with these two transporters. Cytotoxicity and uptake assays confirmed their toxic interaction on P-glycoprotein-overexpressing CEM/ADR5000 and BCRP-overexpressing MDA-MD-231-BCRP cell lines. To specifically visualize the results obtained on the P-glycoprotein inhibitor 2,2’-methylenebis(6-tert-butyl-4-methylphenol), we performed live cell time-lapse microscopy. Confocal fluorescence microscopy was used to understand the behavior of the molecule and the consequences that it has on the uptake of the well-known substrate doxorubicin and, in comparison, with the known inhibitor verapamil. Based on the results, we provide evidence that the compound in question is an inhibitor of the P-glycoprotein. Moreover, it is also possible that 2,2’-methylenebis(6-tert-butyl-4-methylphenol), together with three other compounds, may also inhibit the breast cancer resistance protein. This discovery implies that plastic-related compounds can not only harm the human body but can also inhibit detoxifying efflux pumps, which increases their toxic potential as these transporters lose their physiological functions.</jats:p>
- Autoren
- Matteo Rosellini
- Petri Turunen
- Thomas Efferth
- DOI
- 10.3390/molecules28062710
- eISSN
- 1420-3049
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- Molecules
- Sprache
- en
- Online publication date
- 2023
- Paginierung
- 2710 - 2710
- Status
- Published online
- Herausgeber
- MDPI AG
- Herausgeber URL
- http://dx.doi.org/10.3390/molecules28062710
- Datum der Datenerfassung
- 2023
- Titel
- Impact of Plastic-Related Compounds on P-Glycoprotein and Breast Cancer Resistance Protein In Vitro
- Ausgabe der Zeitschrift
- 28
Datenquelle: Crossref
- Abstract
- Plastic in oceans degrades to microplastics and nanoplastics, causing various problems for marine fauna and flora. Recently, microplastic has been detected in blood, breast milk and placenta, underlining their ability to enter the human body with still unknown effects. In addition, plastic contains other compounds such as plasticizers, antioxidants or lubricants, whose impact on human health is also elusive. On the cellular level, two transporters involved in cell protection and detoxification of xenobiotic compounds are the ABC-transporters P-glycoprotein (P-gp, MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2). Despite the great importance of these proteins to maintain the correct cellular balance, their interaction with plastic and related products is evasive. In this study, the possible interaction between different plastic-related compounds and these two transporters was investigated. Applying virtual compound screening and molecular docking of more than 1000 commercially available plastic compounds, we identified candidates most probably interacting with these two transporters. Cytotoxicity and uptake assays confirmed their toxic interaction on P-glycoprotein-overexpressing CEM/ADR5000 and BCRP-overexpressing MDA-MD-231-BCRP cell lines. To specifically visualize the results obtained on the P-glycoprotein inhibitor 2,2'-methylenebis(6-tert-butyl-4-methylphenol), we performed live cell time-lapse microscopy. Confocal fluorescence microscopy was used to understand the behavior of the molecule and the consequences that it has on the uptake of the well-known substrate doxorubicin and, in comparison, with the known inhibitor verapamil. Based on the results, we provide evidence that the compound in question is an inhibitor of the P-glycoprotein. Moreover, it is also possible that 2,2'-methylenebis(6-tert-butyl-4-methylphenol), together with three other compounds, may also inhibit the breast cancer resistance protein. This discovery implies that plastic-related compounds can not only harm the human body but can also inhibit detoxifying efflux pumps, which increases their toxic potential as these transporters lose their physiological functions.
- Addresses
- Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
- Autoren
- Matteo Rosellini
- Petri Turunen
- Thomas Efferth
- DOI
- 10.3390/molecules28062710
- eISSN
- 1420-3049
- Externe Identifier
- PubMed Identifier: 36985682
- PubMed Central ID: PMC10058098
- Funding acknowledgements
- Deutsche Forschungsgemeinschaft: 497669232
- Deutsche Forschungsgemeinschaft: GRK 2015/2
- Deutsche Forschungsgemeinschaft: project number 497669232
- Open access
- true
- ISSN
- 1420-3049
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- Molecules (Basel, Switzerland)
- Schlüsselwörter
- Humans
- Breast Neoplasms
- Plastics
- Neoplasm Proteins
- Female
- Molecular Docking Simulation
- ATP Binding Cassette Transporter, Subfamily G, Member 2
- ATP Binding Cassette Transporter, Subfamily B
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2023
- Open access status
- Open Access
- Paginierung
- 2710
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2023
- Titel
- Impact of Plastic-Related Compounds on P-Glycoprotein and Breast Cancer Resistance Protein In Vitro.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 28
Files
https://www.mdpi.com/1420-3049/28/6/2710/pdf?version=1679027598 https://europepmc.org/articles/PMC10058098?pdf=render
Datenquelle: Europe PubMed Central
- Abstract
- Plastic in oceans degrades to microplastics and nanoplastics, causing various problems for marine fauna and flora. Recently, microplastic has been detected in blood, breast milk and placenta, underlining their ability to enter the human body with still unknown effects. In addition, plastic contains other compounds such as plasticizers, antioxidants or lubricants, whose impact on human health is also elusive. On the cellular level, two transporters involved in cell protection and detoxification of xenobiotic compounds are the ABC-transporters P-glycoprotein (P-gp, MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2). Despite the great importance of these proteins to maintain the correct cellular balance, their interaction with plastic and related products is evasive. In this study, the possible interaction between different plastic-related compounds and these two transporters was investigated. Applying virtual compound screening and molecular docking of more than 1000 commercially available plastic compounds, we identified candidates most probably interacting with these two transporters. Cytotoxicity and uptake assays confirmed their toxic interaction on P-glycoprotein-overexpressing CEM/ADR5000 and BCRP-overexpressing MDA-MD-231-BCRP cell lines. To specifically visualize the results obtained on the P-glycoprotein inhibitor 2,2'-methylenebis(6-tert-butyl-4-methylphenol), we performed live cell time-lapse microscopy. Confocal fluorescence microscopy was used to understand the behavior of the molecule and the consequences that it has on the uptake of the well-known substrate doxorubicin and, in comparison, with the known inhibitor verapamil. Based on the results, we provide evidence that the compound in question is an inhibitor of the P-glycoprotein. Moreover, it is also possible that 2,2'-methylenebis(6-tert-butyl-4-methylphenol), together with three other compounds, may also inhibit the breast cancer resistance protein. This discovery implies that plastic-related compounds can not only harm the human body but can also inhibit detoxifying efflux pumps, which increases their toxic potential as these transporters lose their physiological functions.
- Date of acceptance
- 2023
- Autoren
- Matteo Rosellini
- Petri Turunen
- Thomas Efferth
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/36985682
- DOI
- 10.3390/molecules28062710
- eISSN
- 1420-3049
- Externe Identifier
- PubMed Central ID: PMC10058098
- Funding acknowledgements
- Deutsche Forschungsgemeinschaft: GRK 2015/2
- Deutsche Forschungsgemeinschaft: project number 497669232
- Ausgabe der Veröffentlichung
- 6
- Zeitschrift
- Molecules
- Schlüsselwörter
- cytotoxicity
- live cell imaging
- microplastic
- microscopy
- plastic
- uptake
- Humans
- Female
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- ATP Binding Cassette Transporter, Subfamily G, Member 2
- Plastics
- Molecular Docking Simulation
- Neoplasm Proteins
- ATP Binding Cassette Transporter, Subfamily B
- Breast Neoplasms
- Sprache
- eng
- Country
- Switzerland
- PII
- molecules28062710
- Datum der Veröffentlichung
- 2023
- Status
- Published online
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2023
- Titel
- Impact of Plastic-Related Compounds on P-Glycoprotein and Breast Cancer Resistance Protein In Vitro.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 28
Datenquelle: PubMed
- Beziehungen:
- Eigentum von