DNA damage independent inhibition of NF-κB transcription by anthracyclines
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10362/147238 |
Resumo: | Funding: We are grateful to the Genomics Unit, Bioinformatics, and the Animal House at IGC. We thank Margarida Gama-Carvalho for the critical revision of the manuscript. This work was supported by the European Commission Horizon 2020 (ERC-2014-CoG 647888-iPROTECTION) and by Fundação para a Ciência e Tecnologia (FCT: PTDC/BIM-MEC/4665/2014 and EXPL/MED-IMU/0620/2021). SW is funded by the Deutsche Forschungsgemeinschaft, DFG, project number WE 4971/6-1, the Excellence Cluster Balance of the Microverse (EXC 2051; 390713860), and the Federal Ministry of Education and Research (BMBF) project number 01EN2001. |
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DNA damage independent inhibition of NF-κB transcription by anthracyclinesanthracyclinescancerDNA damage responseimmunologyinflammationmouseNeuroscience(all)Biochemistry, Genetics and Molecular Biology(all)Immunology and Microbiology(all)SDG 3 - Good Health and Well-beingFunding: We are grateful to the Genomics Unit, Bioinformatics, and the Animal House at IGC. We thank Margarida Gama-Carvalho for the critical revision of the manuscript. This work was supported by the European Commission Horizon 2020 (ERC-2014-CoG 647888-iPROTECTION) and by Fundação para a Ciência e Tecnologia (FCT: PTDC/BIM-MEC/4665/2014 and EXPL/MED-IMU/0620/2021). SW is funded by the Deutsche Forschungsgemeinschaft, DFG, project number WE 4971/6-1, the Excellence Cluster Balance of the Microverse (EXC 2051; 390713860), and the Federal Ministry of Education and Research (BMBF) project number 01EN2001.Anthracyclines are among the most used and effective anticancer drugs. Their activity has been attributed to DNA double-strand breaks resulting from topoisomerase II poisoning and to eviction of histones from select sites in the genome. Here, we show that the extensively used anthracyclines Doxorubicin, Daunorubicin, and Epirubicin decrease the transcription of nuclear factor kappa B (NF-κB)-dependent gene targets, but not interferon-responsive genes in primary mouse (Mus musculus) macrophages. Using an NMR-based structural approach, we demonstrate that anthracyclines disturb the complexes formed between the NF-κB subunit RelA and its DNA-binding sites. The anthracycline variants Aclarubicin, Doxorubicinone, and the newly developed Dimethyl-doxorubicin, which share anticancer properties with the other anthracyclines but do not induce DNA damage, also suppressed inflammation, thus uncoupling DNA damage from the effects on inflammation. These findings have implications for anticancer therapy and for the development of novel anti-inflammatory drugs with limited side effects for life-threatening conditions such as sepsis.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNChora, Angelo FerreiraPedroso, DoraKyriakou, EleniPejanovic, NadjaColaço, HenriqueGozzelino, RaffaellaBarros, AndréWillmann, KatharinaVelho, TiagoMoita, Catarina F.Santos, IsaPereira, PedroCarvalho, SilviaMartins, Filipa BatalhaFerreira, João A.de Almeida, Sérgio FernandesBenes, VladimirAnrather, JosefWeis, SebastianSoares, Miguel P.Geerlof, ArieNeefjes, JacquesSattler, MichaelMessias, Ana C.Neves-Costa, AnaMoita, Luis Ferreira2023-01-09T22:16:36Z2022-12-072022-12-07T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/147238eng2050-084XPURE: 49545246https://doi.org/10.7554/eLife.77443info: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:RCAAP2024-05-22T18:07:54Zoai:run.unl.pt:10362/147238Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-22T18:07:54Repositório 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 |
DNA damage independent inhibition of NF-κB transcription by anthracyclines |
| title |
DNA damage independent inhibition of NF-κB transcription by anthracyclines |
| spellingShingle |
DNA damage independent inhibition of NF-κB transcription by anthracyclines Chora, Angelo Ferreira anthracyclines cancer DNA damage response immunology inflammation mouse Neuroscience(all) Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) SDG 3 - Good Health and Well-being |
| title_short |
DNA damage independent inhibition of NF-κB transcription by anthracyclines |
| title_full |
DNA damage independent inhibition of NF-κB transcription by anthracyclines |
| title_fullStr |
DNA damage independent inhibition of NF-κB transcription by anthracyclines |
| title_full_unstemmed |
DNA damage independent inhibition of NF-κB transcription by anthracyclines |
| title_sort |
DNA damage independent inhibition of NF-κB transcription by anthracyclines |
| author |
Chora, Angelo Ferreira |
| author_facet |
Chora, Angelo Ferreira Pedroso, Dora Kyriakou, Eleni Pejanovic, Nadja Colaço, Henrique Gozzelino, Raffaella Barros, André Willmann, Katharina Velho, Tiago Moita, Catarina F. Santos, Isa Pereira, Pedro Carvalho, Silvia Martins, Filipa Batalha Ferreira, João A. de Almeida, Sérgio Fernandes Benes, Vladimir Anrather, Josef Weis, Sebastian Soares, Miguel P. Geerlof, Arie Neefjes, Jacques Sattler, Michael Messias, Ana C. Neves-Costa, Ana Moita, Luis Ferreira |
| author_role |
author |
| author2 |
Pedroso, Dora Kyriakou, Eleni Pejanovic, Nadja Colaço, Henrique Gozzelino, Raffaella Barros, André Willmann, Katharina Velho, Tiago Moita, Catarina F. Santos, Isa Pereira, Pedro Carvalho, Silvia Martins, Filipa Batalha Ferreira, João A. de Almeida, Sérgio Fernandes Benes, Vladimir Anrather, Josef Weis, Sebastian Soares, Miguel P. Geerlof, Arie Neefjes, Jacques Sattler, Michael Messias, Ana C. Neves-Costa, Ana Moita, Luis Ferreira |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) RUN |
| dc.contributor.author.fl_str_mv |
Chora, Angelo Ferreira Pedroso, Dora Kyriakou, Eleni Pejanovic, Nadja Colaço, Henrique Gozzelino, Raffaella Barros, André Willmann, Katharina Velho, Tiago Moita, Catarina F. Santos, Isa Pereira, Pedro Carvalho, Silvia Martins, Filipa Batalha Ferreira, João A. de Almeida, Sérgio Fernandes Benes, Vladimir Anrather, Josef Weis, Sebastian Soares, Miguel P. Geerlof, Arie Neefjes, Jacques Sattler, Michael Messias, Ana C. Neves-Costa, Ana Moita, Luis Ferreira |
| dc.subject.por.fl_str_mv |
anthracyclines cancer DNA damage response immunology inflammation mouse Neuroscience(all) Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) SDG 3 - Good Health and Well-being |
| topic |
anthracyclines cancer DNA damage response immunology inflammation mouse Neuroscience(all) Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) SDG 3 - Good Health and Well-being |
| description |
Funding: We are grateful to the Genomics Unit, Bioinformatics, and the Animal House at IGC. We thank Margarida Gama-Carvalho for the critical revision of the manuscript. This work was supported by the European Commission Horizon 2020 (ERC-2014-CoG 647888-iPROTECTION) and by Fundação para a Ciência e Tecnologia (FCT: PTDC/BIM-MEC/4665/2014 and EXPL/MED-IMU/0620/2021). SW is funded by the Deutsche Forschungsgemeinschaft, DFG, project number WE 4971/6-1, the Excellence Cluster Balance of the Microverse (EXC 2051; 390713860), and the Federal Ministry of Education and Research (BMBF) project number 01EN2001. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-12-07 2022-12-07T00:00:00Z 2023-01-09T22:16:36Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/147238 |
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http://hdl.handle.net/10362/147238 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
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2050-084X PURE: 49545246 https://doi.org/10.7554/eLife.77443 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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