The Complex Dynamic of Phase I Drug Metabolism in the Early Stages of Doxorubicin Resistance in Breast Cancer Cells

Detalhes bibliográficos
Autor(a) principal: Barata, Isabel S
Data de Publicação: 2022
Outros Autores: Gomes, Bruno C, Rodrigues, António S, Rueff, José, Kranendonk, Michel, Esteves, Francisco
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/145580
Resumo: Funding: This research was partly funded by the Research Center grant ToxOmics (UIDB/00009/2020 and UIDP/0009/2020), from the Portuguese Fundação para a Ciência e a Tecnologia—FCT
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spelling The Complex Dynamic of Phase I Drug Metabolism in the Early Stages of Doxorubicin Resistance in Breast Cancer CellsDrug Resistance, Neoplasm/geneticsCytochrome P-450 CYP3A/geneticsDoxorubicin/pharmacologyAntibiotics, Antineoplastic/pharmacologyNeoplasmsSDG 3 - Good Health and Well-beingFunding: This research was partly funded by the Research Center grant ToxOmics (UIDB/00009/2020 and UIDP/0009/2020), from the Portuguese Fundação para a Ciência e a Tecnologia—FCTThe altered activity of drug metabolism enzymes (DMEs) is a hallmark of chemotherapy resistance. Cytochrome P450s (CYPs), mainly CYP3A4, and several oxidoreductases are responsible for Phase I metabolism of doxorubicin (DOX), an anthracycline widely used in breast cancer (BC) treatment. This study aimed to investigate the role of Phase I DMEs involved in the first stages of acquisition of DOX-resistance in BC cells. For this purpose, the expression of 92 DME genes and specific CYP-complex enzymes activities were assessed in either sensitive (MCF-7 parental cells; MCF-7/DOXS) or DOX-resistant (MCF-7/DOXR) cells. The DMEs genes detected to be significantly differentially expressed in MCF-7/DOXR cells (12 CYPs and eight oxidoreductases) were indicated previously to be involved in tumor progression and/or chemotherapy response. The analysis of CYP-mediated activities suggests a putative enhanced CYP3A4-dependent metabolism in MCF-7/DOXR cells. A discrepancy was observed between CYP-enzyme activities and their corresponding levels of mRNA transcripts. This is indicative that the phenotype of DMEs is not linearly correlated with transcription induction responses, confirming the multifactorial complexity of this mechanism. Our results pinpoint the potential role of specific CYPs and oxidoreductases involved in the metabolism of drugs, retinoic and arachidonic acids, in the mechanisms of chemo-resistance to DOX and carcinogenesis of BC.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centre for Toxicogenomics and Human Health (ToxOmics)RUNBarata, Isabel SGomes, Bruno CRodrigues, António SRueff, JoséKranendonk, MichelEsteves, Francisco2022-11-16T22:10:46Z2022-10-292022-10-29T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/145580eng0920-8569PURE: 47765572https://doi.org/10.3390/genes13111977info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:26:05Zoai:run.unl.pt:10362/145580Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:52:09.672064Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv The Complex Dynamic of Phase I Drug Metabolism in the Early Stages of Doxorubicin Resistance in Breast Cancer Cells
title The Complex Dynamic of Phase I Drug Metabolism in the Early Stages of Doxorubicin Resistance in Breast Cancer Cells
spellingShingle The Complex Dynamic of Phase I Drug Metabolism in the Early Stages of Doxorubicin Resistance in Breast Cancer Cells
Barata, Isabel S
Drug Resistance, Neoplasm/genetics
Cytochrome P-450 CYP3A/genetics
Doxorubicin/pharmacology
Antibiotics, Antineoplastic/pharmacology
Neoplasms
SDG 3 - Good Health and Well-being
title_short The Complex Dynamic of Phase I Drug Metabolism in the Early Stages of Doxorubicin Resistance in Breast Cancer Cells
title_full The Complex Dynamic of Phase I Drug Metabolism in the Early Stages of Doxorubicin Resistance in Breast Cancer Cells
title_fullStr The Complex Dynamic of Phase I Drug Metabolism in the Early Stages of Doxorubicin Resistance in Breast Cancer Cells
title_full_unstemmed The Complex Dynamic of Phase I Drug Metabolism in the Early Stages of Doxorubicin Resistance in Breast Cancer Cells
title_sort The Complex Dynamic of Phase I Drug Metabolism in the Early Stages of Doxorubicin Resistance in Breast Cancer Cells
author Barata, Isabel S
author_facet Barata, Isabel S
Gomes, Bruno C
Rodrigues, António S
Rueff, José
Kranendonk, Michel
Esteves, Francisco
author_role author
author2 Gomes, Bruno C
Rodrigues, António S
Rueff, José
Kranendonk, Michel
Esteves, Francisco
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Centre for Toxicogenomics and Human Health (ToxOmics)
RUN
dc.contributor.author.fl_str_mv Barata, Isabel S
Gomes, Bruno C
Rodrigues, António S
Rueff, José
Kranendonk, Michel
Esteves, Francisco
dc.subject.por.fl_str_mv Drug Resistance, Neoplasm/genetics
Cytochrome P-450 CYP3A/genetics
Doxorubicin/pharmacology
Antibiotics, Antineoplastic/pharmacology
Neoplasms
SDG 3 - Good Health and Well-being
topic Drug Resistance, Neoplasm/genetics
Cytochrome P-450 CYP3A/genetics
Doxorubicin/pharmacology
Antibiotics, Antineoplastic/pharmacology
Neoplasms
SDG 3 - Good Health and Well-being
description Funding: This research was partly funded by the Research Center grant ToxOmics (UIDB/00009/2020 and UIDP/0009/2020), from the Portuguese Fundação para a Ciência e a Tecnologia—FCT
publishDate 2022
dc.date.none.fl_str_mv 2022-11-16T22:10:46Z
2022-10-29
2022-10-29T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/145580
url http://hdl.handle.net/10362/145580
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0920-8569
PURE: 47765572
https://doi.org/10.3390/genes13111977
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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