Differences in the mechanisms of action of BDE-47 and its metabolites on OVCAR-3 and MCF-7 cell apoptosis
PBN-AR
Instytucja
Wydział Hodowli i Biologii Zwierząt (Uniwersytet Rolniczy im. Hugona Kołłątaja w Krakowie)
Informacje podstawowe
Główny język publikacji
en
Czasopismo
Journal of Applied Toxicology (30pkt w roku publikacji)
ISSN
0260-437X
EISSN
Wydawca
DOI
URL
Rok publikacji
2017
Numer zeszytu
4
Strony od-do
426-435
Numer tomu
37
Identyfikator DOI
Liczba arkuszy
0.5
Autorzy
(liczba autorów: 2)
Pozostali autorzy
+ 1
Autorzy przekładu
(liczba autorów przekładu: 0)
Słowa kluczowe
en
apoptosis; BDE-47; hydroxylated metabolites; MCF-7; OVCAR-3
Streszczenia
Język
en
Treść
Data concerning possible carcinogenic action of polybrominated diphenyl ethers (PBDEs) in hormone-dependent tissues are limited. Our earlier studies showed that 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) stimulated OVCAR-3 and MCF-7 cell proliferation, while its hydroxylated metabolites (5-OH-BDE-47 and 6-OH-BDE-47) increased estrogen receptors protein expression and extracellular signal-regulated kinase 1/2 and protein kinase Cα phosphorylation in these cell lines. In addition to cell proliferative disorder, a failure in the regulation of apoptosis can also lead to the formation and development of tumors. Therefore, in the present study, we investigated the effect of BDE-47 and its metabolites (2.5–50 ng ml–1) on the expression of apoptosis regulatory genes and proteins, caspase-8 and -9 activity and DNA fragmentation induced by extracellular signal-regulated kinase inhibitor (PD098059) and protein kinase Cα inhibitor (Gӧ 6976) in ovarian (OVCAR-3) and breast (MCF-7) cancer cells. In OVCAR-3 cells, BDE-47 upregulated expression of most of the investigated genes and increased protein expression of tumor necrosis factor (TNF)-α, TNF receptor 1, caspase-6, Bcl-xl and caspase-8 activity. Whereas in MCF-7 cells, BDE-47 resulted in the downregulation of most of the investigated genes, and decreased caspase-8 and -9 activity. In both OVCAR-3 and MCF-7 cells, the expression of most of the investigated genes were downregulated by metabolites. Exposure of OVCAR-3 cells to 5-OH-BDE-47 corresponded with a decrease in the protein expression of caspase-6, caspase-9 and Bcl-xl and treatment with 6-OH-BDE-47 decreased Bcl-xl and TNF receptor 1 expression in OVCAR-3 cells and caspase-9 expression in MCF-7 cells. Hydroxylated metabolites of BDE-47 have strong inhibitory effects on apoptosis in ovarian and breast tumor cells and thus should be considered potential carcinogens in hormone-dependent cancers. Copyright © 2016 John Wiley & Sons, Ltd.
Inne
System-identifier
UR427bad5b217a468f9cec472117de2d6c
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