Journal
MOLECULES
Volume 26, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/molecules26040995
Keywords
PBDE; Dysidea sp.; anticancer; apoptosis; intrinsic mitochondrial pathway; P01F08
Funding
- Deutsche Forschungsgemeinschaft [270650915/RTG 2158, RTG 2578]
- Dusseldorf School of Oncology - Comprehensive Cancer Center Dusseldorf/Deutsche Krebshilfe
- Medical Faculty of the Heinrich Heine University Dusseldorf
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This article summarizes the research progress of polybrominated diphenyl ethers (PBDEs), including their sources, structure-activity relationships, environmental toxicology studies, and a promising anticancer therapeutic PBDE. The study found that P01F08 induces apoptosis through the intrinsic mitochondrial pathway, showing cytotoxicity and apoptosis induction capacity in Ramos and Jurkat lymphoma cells.
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 mu M 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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