title: Different mechanisms of action of 2, 2', 4, 4'-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.
abstract: 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 50 ng ml-1) on proliferation (BrdU), cell-cycle genes (real-time PCR) and protein expression (Western blot), protein expression of oestrogen receptors (α β), extracellular signal-regulated kinases 1 and 2 (ERK1/2) and protein kinase Cα (PKCα) 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 ERα and ERβ protein expression and ERK1/2 and PKCα phosphorylation. Metabolites had no effect on cell proliferation but increased both ERs protein expression and ERK1/2 and PKCα phosphorylation. In MCF-7 cells, the parent compound displayed no effect on cell proliferation but decreased ERα and increased ERβ protein expression with concomitant induction of PKCα phosphorylation. Both metabolites increased MCF-7 cell proliferation, ERK1/2 and PKCα phosphorylation and decreased ERα and ERβ 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 © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Physiology and Toxicology of Reproduction, Institute of Zoology, Jagiellonian University in Krakow, Krakow, Poland. a.karpeta@ur.krakow.pl.|Department of Animal Physiology and Endocrinology, University of Agriculture in Krakow, Poland. a.karpeta@ur.krakow.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Karpeta
authors.affiliation: Department of Physiology and Toxicology of Reproduction, Institute of Zoology, Jagiellonian University in Krakow, Krakow, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Maniecka
authors.affiliation: Department of Physiology and Toxicology of Reproduction, Institute of Zoology, Jagiellonian University in Krakow, Krakow, Poland.
authors.forename: Ewa Łucja
authors.initials: EŁ
authors.lastname: Gregoraszczuk
mesh_terms: D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D047628:Estrogen Receptor alpha / Q000235:genetics; D047629:Estrogen Receptor beta / Q000187:drug effects; D005260:Female; D018816:Genes, cdc / Q000187:drug effects; D055768:Halogenated Diphenyl Ethers / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D061986:MCF-7 Cells; D010051:Ovarian Neoplasms / Q000473:pathology; D010766:Phosphorylation; D011075:Polybrominated Biphenyls / Q000378:metabolism / Q000633:toxicity*; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C580598:5-OH-BDE-47; C580599:6-OH-BDE-47; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D055768:Halogenated Diphenyl Ethers; D011075:Polybrominated Biphenyls; C511295:2,2',4,4'-tetrabromodiphenyl ether; D051571:Protein Kinase C-alpha
keywords: BDE-47; MCF-7; OVCAR-3; hydroxylated metabolites; proliferation