Mechanisms of cell death induced by hexabromocyclododecane (HBCD) involves apoptosis, autophagy, and ER stress
Mohammed, Noor A. Lewis, Kirstie Hodges, Nikolas Michelangeli, Francesco
Mohammed, Noor A.
Lewis, Kirstie
Hodges, Nikolas
Michelangeli, Francesco
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EPub Date
Publication Date
2023-06-13
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Abstract
Hexabromocyclododecane (HBCD), was a widely utilized brominated flame retardant, commonly found in a wide range of household products. The pervasiveness of HBCD has identified the presence of this chemical in foods and in human tissues. Therefore, HBCD has been identified as a chemical of concern. The aim was to investigate the degree of cytotoxicity of HBCD in a range of cell lines derived from different tissues, (including hematopoietic, nerve, liver, and kidney-derived cells) with a view of determining any differential cell type effects. In addition, this study also investigated the mechanism(s) by which HBCD could cause cell death. The results showed that HCBD was considerably more toxic to leukocyte-derived (RBL2H3) and neuronal-derived (SHSY-5Y) cells with LC50 values of 1.5 and 6.1 µM, respectively, compared to cells derived from liver (HepG2) and kidney (Cos-7), which had LC50 values of 28.5 and 17.5 µM, respectively. A detailed investigation of the mechanism(s) of cell death showed that HBCD caused, at least in part, Ca2+-dependent cell death, caspase-activated apoptosis, and autophagy, but there was little evidence for either necrosis or necroptosis occurring. Furthermore, it was shown that HBCD can also induce the ER stress response which is a known trigger of both apoptosis and autophagy and therefore this could be one of the crucial events by which cell death is initiated. As each of these cell death mechanisms was investigated in at least two different cell lines and no differences were identified, it is likely that the mode of action is not cell-type specific.
Citation
Mohammed, N. A., Lewis, K., Hodges, N., & Michelangeli, F. (2023). Mechanisms of cell death induced by hexabromocyclododecane (HBCD) involves apoptosis, autophagy, and ER stress. Journal of Biochemical and Molecular Toxicology, vol(issue), e23397. https://doi.org/10.1002/jbt.23397
Publisher
Wiley
Journal
Journal of Biochemical and Molecular Toxicology
Research Unit
DOI
10.1002/jbt.23397
PubMed ID
PubMed Central ID
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Article
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Series/Report no.
ISSN
1095-6670
EISSN
1099-0461