Different mechanisms of action of 2, 2%26apos;, 4, 4%26apos;-tetrabromodiphenyl ether (BDE-47) and its metabolites (5-OH-BDE-47 and 6-OH-BDE-47) on cell proliferation in OVCAR-3 ovarian cancer cells and MCF-7 breast cancer cells

作者：Karpeta Anna; Maniecka Anna; Gregoraszczuk Ewa Lucja

来源：Journal of Applied Toxicology, 2016, 36(12): 1558-1567.

DOI：10.1002/jat.3316

• BDE-47
• hydroxylated metabolites
• OVCAR-3
• MCF-7
• proliferation

Data concerning the possible action of polybrominated diphenyl ethers (PBDEs) in hormone-dependent cancer are scarce. Some data showed that PBDEs may directly affect breast cancer cells formation and only one research showed increased proliferation of the OVCAR-3 cells, but the results are ambiguous and the mechanisms are not clear. There is growing evidence that not only parent compounds but also its metabolites may be involved in cancer development. The present study was, therefore, designed to determine the effect of BDE-47 and its metabolites (2.5 to 50ngml(-1)) on proliferation (BrdU), cell-cycle genes (real-time PCR) and protein expression (Western blot), protein expression of oestrogen receptors ( ), extracellular signal-regulated kinases 1 and 2 (ERK1/2) and protein kinase C (PKC) in OVCAR-3 ovarian and MCF-7 breast cancer cells. In OVCAR-3 cells, the parent compound stimulated cell proliferation by activating CDK1, CDK7, E2F1 and E2F2. Independent of time of exposure, BDE-47 had no effect on ER and ER protein expression and ERK1/2 and PKC phosphorylation. Metabolites had no effect on cell proliferation but increased both ERs protein expression and ERK1/2 and PKC phosphorylation. In MCF-7 cells, the parent compound displayed no effect on cell proliferation but decreased ER and increased ER protein expression with concomitant induction of PKC phosphorylation. Both metabolites increased MCF-7 cell proliferation, ERK1/2 and PKC phosphorylation and decreased ER and ER protein expression.We suggest that studies concerning PBDEs with fewer bromine atoms should be continued to understand environmental links to different hormone-dependent cancers. Copyright (c) 2016 John Wiley & Sons, Ltd.
In present study, we investigated the influence of BDE-47 and its metabolites on proliferation in OVCAR-3 ovarian and MCF-7 breast cancer cells by examining their effects on cell-cycle regulation, oestrogen receptors expression and activation of ERK1/2 and PKC phosphorylation. The results clearly show a tissue-dependent mechanism of BDE-47 action. BDE-47 increased cell-cycle genes and proteins expression in OVCAR-3, but not in MCF-7 cells. Hydroxylated metabolites in both cell lines acted on ERs expression and ERK1/2 and PKC phosphorylation.

• 出版日期2016-12