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Environmentally relevant concentrations of Bisphenol A interact with doxorubicin transcriptional effects in human cell lines

2019-08Journal article Open access
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dc.contributor.authorRibeiro, Edna
dc.contributor.authorDelgadinho, Mariana
dc.contributor.authorBrito, Miguel
dc.date.accessioned2019-08-30T15:10:23Z
dc.date.available2019-08-30T15:10:23Z
dc.date.issued2019-08
dc.description.abstractThe worldwide production of synthetic chemicals, including endocrine disruptor chemicals (EDCs), such as Bisphenol A (BPA) has increased significantly in the last two decades. Human exposure to BPA, particularly through ingestion, is continuous and ubiquitous. Although considered a weak environmental estrogen, BPA can induce divergent biological responses through several signaling pathways, including carcinogenesis in hormone-responsive organs. However, and despite the continuous increase of tumor cell-resistance to therapeutic drugs, such as doxorubicin (DOX), information regarding BPA drug interactions is still scarce, although its potential role in chemo-resistance has been suggested. This study aims to assess the potential interactions between environmentally relevant levels of BPA and DOX at a therapeutic dosage on Hep-2 and MRC-5 cell lines transcriptome. Transcriptional effects in key-player genes for cancer biology, namely c-fos, p21, and bcl-xl, were evaluated through qRT-PCR. The cellular response was analyzed after exposure to BPA, DOX, or co-exposure to both chemicals. Transcriptional analysis showed that BPA exposure induces upregulation of bcl-xl and endorses an antagonistic non-monotonic response on DOX transcriptional effects. Moreover, the BPA interaction with DOX on c-fos and p21 expression emphasize its cellular specificity and divergent effects. Overall, Hep-2 was more susceptible to BPA effects in a dose-dependent manner while MRC-5 transcriptional levels endorsed a non-monotonic response. Our data indicate that BPA environmental exposure may influence chemotherapy outcomes, which emphasize the urgency for a better understanding of BPA interactions with chemotherapeutic agents, in the context of risk assessment.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationRibeiro E, Delgadinho M, Brito M. Environmentally relevant concentrations of Bisphenol A interact with doxorubicin transcriptional effects in human cell lines. Toxics. 2019;7(3):43.pt_PT
dc.identifier.doi10.3390/toxics7030043pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.21/10445
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relation.publisherversionhttps://www.mdpi.com/2305-6304/7/3/43/htmpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectBisphenol Apt_PT
dc.subjectDoxorubicinpt_PT
dc.subjectHep-2 cell linept_PT
dc.subjectMRC-5 cell linept_PT
dc.subjectDrug interactionpt_PT
dc.subjectGene transcriptionpt_PT
dc.titleEnvironmentally relevant concentrations of Bisphenol A interact with doxorubicin transcriptional effects in human cell linespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue3pt_PT
oaire.citation.startPage43pt_PT
oaire.citation.titleToxicspt_PT
oaire.citation.volume7pt_PT
person.familyNameRibeiro
person.familyNameBrito
person.givenNameEdna
person.givenNameMiguel
person.identifier.ciencia-idC414-CDF2-D35A
person.identifier.ciencia-id231F-F341-7E93
person.identifier.orcid0000-0003-1316-7750
person.identifier.orcid0000-0001-6394-658X
person.identifier.ridA-7970-2016
person.identifier.scopus-author-id35224551000
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationa571bf34-bcda-49ca-b5cb-4cdecbb3d9c7
relation.isAuthorOfPublication4252d8e0-800c-4d67-8b13-0b711d860669
relation.isAuthorOfPublication.latestForDiscoverya571bf34-bcda-49ca-b5cb-4cdecbb3d9c7

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