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40 Years of Research on Polybrominated Diphenyl Ethers (PBDEs)—A Historical Overview and Newest Data of a Promising Anticancer Drug

Polybrominated diphenyl ethers (PBDEs) are a group of molecules with an ambiguous background in literature. PBDEs were first isolated from marine sponges of Dysidea species in 1981 and have been under continuous research to the present day. This article summarizes the two research aspects, (i) the m...

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Autores principales: Schmitt, Laura, Hinxlage, Ilka, Cea, Pablo A., Gohlke, Holger, Wesselborg, Sebastian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918430/
https://www.ncbi.nlm.nih.gov/pubmed/33668501
http://dx.doi.org/10.3390/molecules26040995
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author Schmitt, Laura
Hinxlage, Ilka
Cea, Pablo A.
Gohlke, Holger
Wesselborg, Sebastian
author_facet Schmitt, Laura
Hinxlage, Ilka
Cea, Pablo A.
Gohlke, Holger
Wesselborg, Sebastian
author_sort Schmitt, Laura
collection PubMed
description Polybrominated diphenyl ethers (PBDEs) are a group of molecules with an ambiguous background in literature. PBDEs were first isolated from marine sponges of Dysidea species in 1981 and have been under continuous research to the present day. This article summarizes the two research aspects, (i) the marine compound chemistry research dealing with naturally produced PBDEs and (ii) the environmental toxicology research dealing with synthetically-produced brominated flame-retardant PBDEs. The different bioactivity patterns are set in relation to the structural similarities and dissimilarities between both groups. In addition, this article gives a first structure–activity relationship analysis comparing both groups of PBDEs. Moreover, we provide novel data of a promising anticancer therapeutic PBDE (i.e., 4,5,6-tribromo-2-(2′,4′-dibromophenoxy)phenol; termed P01F08). It has been known since 1995 that P01F08 exhibits anticancer activity, but the detailed mechanism remains poorly understood. Only recently, Mayer and colleagues identified a therapeutic window for P01F08, specifically targeting primary malignant cells in a low µM range. To elucidate the mechanistic pathway of cell death induction, we verified and compared its cytotoxicity and apoptosis induction capacity in Ramos and Jurkat lymphoma cells. Moreover, using Jurkat cells overexpressing antiapoptotic Bcl-2, we were able to show that P01F08 induces apoptosis mainly through the intrinsic mitochondrial pathway.
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spelling pubmed-79184302021-03-02 40 Years of Research on Polybrominated Diphenyl Ethers (PBDEs)—A Historical Overview and Newest Data of a Promising Anticancer Drug Schmitt, Laura Hinxlage, Ilka Cea, Pablo A. Gohlke, Holger Wesselborg, Sebastian Molecules Article Polybrominated diphenyl ethers (PBDEs) are a group of molecules with an ambiguous background in literature. PBDEs were first isolated from marine sponges of Dysidea species in 1981 and have been under continuous research to the present day. This article summarizes the two research aspects, (i) the marine compound chemistry research dealing with naturally produced PBDEs and (ii) the environmental toxicology research dealing with synthetically-produced brominated flame-retardant PBDEs. The different bioactivity patterns are set in relation to the structural similarities and dissimilarities between both groups. In addition, this article gives a first structure–activity relationship analysis comparing both groups of PBDEs. Moreover, we provide novel data of a promising anticancer therapeutic PBDE (i.e., 4,5,6-tribromo-2-(2′,4′-dibromophenoxy)phenol; termed P01F08). It has been known since 1995 that P01F08 exhibits anticancer activity, but the detailed mechanism remains poorly understood. Only recently, Mayer and colleagues identified a therapeutic window for P01F08, specifically targeting primary malignant cells in a low µM range. To elucidate the mechanistic pathway of cell death induction, we verified and compared its cytotoxicity and apoptosis induction capacity in Ramos and Jurkat lymphoma cells. Moreover, using Jurkat cells overexpressing antiapoptotic Bcl-2, we were able to show that P01F08 induces apoptosis mainly through the intrinsic mitochondrial pathway. MDPI 2021-02-13 /pmc/articles/PMC7918430/ /pubmed/33668501 http://dx.doi.org/10.3390/molecules26040995 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schmitt, Laura
Hinxlage, Ilka
Cea, Pablo A.
Gohlke, Holger
Wesselborg, Sebastian
40 Years of Research on Polybrominated Diphenyl Ethers (PBDEs)—A Historical Overview and Newest Data of a Promising Anticancer Drug
title 40 Years of Research on Polybrominated Diphenyl Ethers (PBDEs)—A Historical Overview and Newest Data of a Promising Anticancer Drug
title_full 40 Years of Research on Polybrominated Diphenyl Ethers (PBDEs)—A Historical Overview and Newest Data of a Promising Anticancer Drug
title_fullStr 40 Years of Research on Polybrominated Diphenyl Ethers (PBDEs)—A Historical Overview and Newest Data of a Promising Anticancer Drug
title_full_unstemmed 40 Years of Research on Polybrominated Diphenyl Ethers (PBDEs)—A Historical Overview and Newest Data of a Promising Anticancer Drug
title_short 40 Years of Research on Polybrominated Diphenyl Ethers (PBDEs)—A Historical Overview and Newest Data of a Promising Anticancer Drug
title_sort 40 years of research on polybrominated diphenyl ethers (pbdes)—a historical overview and newest data of a promising anticancer drug
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918430/
https://www.ncbi.nlm.nih.gov/pubmed/33668501
http://dx.doi.org/10.3390/molecules26040995
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