The Activation of Endothelial Cells Relies on a Ferroptosis-Like Mechanism
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| 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/10362/119581 |
Resumo: | Funding: The project was funded by IPOLFG EPE and by iNOVA4Health (UID/Multi/04462/2019) a program financially supported by Fundação para a Ciência e Tecnologia (FCT)/Ministério da Educação e Ciência, through national funds. We also acknowledge funding from FCT-MCTES through the project DREAM—PTDC/MEC-ONC/29327/2017. FL-C PhD fellowship was funded by FCT (PD/BD/128337/2017). |
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The Activation of Endothelial Cells Relies on a Ferroptosis-Like MechanismNovel Perspectives in Management of Angiogenesis and Cancer Therapyangiogenesisendothelial cell hyperactivationferroptosislipid peroxidationoxidative stresspolyurea dendrimerspropranololtumor vasculature stabilizersOncologyCancer ResearchSDG 3 - Good Health and Well-beingFunding: The project was funded by IPOLFG EPE and by iNOVA4Health (UID/Multi/04462/2019) a program financially supported by Fundação para a Ciência e Tecnologia (FCT)/Ministério da Educação e Ciência, through national funds. We also acknowledge funding from FCT-MCTES through the project DREAM—PTDC/MEC-ONC/29327/2017. FL-C PhD fellowship was funded by FCT (PD/BD/128337/2017).The activation of endothelial cells (ECs) is a crucial step on the road map of tumor angiogenesis and expanding evidence indicates that a pro-oxidant tumor microenvironment, conditioned by cancer metabolic rewiring, is a relevant controller of this process. Herein, we investigated the contribution of oxidative stress-induced ferroptosis to ECs activation. Moreover, we also addressed the anti-angiogenic effect of Propranolol. We observed that a ferroptosis-like mechanism, induced by xCT inhibition with Erastin, at a non-lethal level, promoted features of ECs activation, such as proliferation, migration and vessel-like structures formation, concomitantly with the depletion of reduced glutathione (GSH) and increased levels of oxidative stress and lipid peroxides. Additionally, this ferroptosis-like mechanism promoted vascular endothelial cadherin (VE-cadherin) junctional gaps and potentiated cancer cell adhesion to ECs and transendothelial migration. Propranolol was able to revert Erastin-dependent activation of ECs and increased levels of hydrogen sulfide (H2S) underlie the mechanism of action of Propranolol. Furthermore, we tested a dual-effect therapy by promoting ECs stability with Propranolol and boosting oxidative stress to induce cancer cell death with a nanoformulation comprising selenium-containing chrysin (SeChry) encapsulated in a fourth generation polyurea dendrimer (SeChry@PUREG4). Our data showed that novel developments in cancer treatment may rely on multi-targeting strategies focusing on nanoformulations for a safer induction of cancer cell death, taking advantage of tumor vasculature stabilization.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNLopes-Coelho, FilipaMartins, FilipaHipólito, AnaMendes, CindySequeira, Catarina O.Pires, Rita F.Almeida, António M.Bonifácio, Vasco D.B.Pereira, Sofia A.Serpa, Jacinta2021-06-18T22:25:53Z2021-05-102021-05-10T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/119581eng2234-943XPURE: 31841566https://doi.org/10.3389/fonc.2021.656229info: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:RCAAP2024-03-11T05:02:11Zoai:run.unl.pt:10362/119581Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:44:08.057203Repositório 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 Activation of Endothelial Cells Relies on a Ferroptosis-Like Mechanism Novel Perspectives in Management of Angiogenesis and Cancer Therapy |
| title |
The Activation of Endothelial Cells Relies on a Ferroptosis-Like Mechanism |
| spellingShingle |
The Activation of Endothelial Cells Relies on a Ferroptosis-Like Mechanism Lopes-Coelho, Filipa angiogenesis endothelial cell hyperactivation ferroptosis lipid peroxidation oxidative stress polyurea dendrimers propranolol tumor vasculature stabilizers Oncology Cancer Research SDG 3 - Good Health and Well-being |
| title_short |
The Activation of Endothelial Cells Relies on a Ferroptosis-Like Mechanism |
| title_full |
The Activation of Endothelial Cells Relies on a Ferroptosis-Like Mechanism |
| title_fullStr |
The Activation of Endothelial Cells Relies on a Ferroptosis-Like Mechanism |
| title_full_unstemmed |
The Activation of Endothelial Cells Relies on a Ferroptosis-Like Mechanism |
| title_sort |
The Activation of Endothelial Cells Relies on a Ferroptosis-Like Mechanism |
| author |
Lopes-Coelho, Filipa |
| author_facet |
Lopes-Coelho, Filipa Martins, Filipa Hipólito, Ana Mendes, Cindy Sequeira, Catarina O. Pires, Rita F. Almeida, António M. Bonifácio, Vasco D.B. Pereira, Sofia A. Serpa, Jacinta |
| author_role |
author |
| author2 |
Martins, Filipa Hipólito, Ana Mendes, Cindy Sequeira, Catarina O. Pires, Rita F. Almeida, António M. Bonifácio, Vasco D.B. Pereira, Sofia A. Serpa, Jacinta |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) Centro de Estudos de Doenças Crónicas (CEDOC) RUN |
| dc.contributor.author.fl_str_mv |
Lopes-Coelho, Filipa Martins, Filipa Hipólito, Ana Mendes, Cindy Sequeira, Catarina O. Pires, Rita F. Almeida, António M. Bonifácio, Vasco D.B. Pereira, Sofia A. Serpa, Jacinta |
| dc.subject.por.fl_str_mv |
angiogenesis endothelial cell hyperactivation ferroptosis lipid peroxidation oxidative stress polyurea dendrimers propranolol tumor vasculature stabilizers Oncology Cancer Research SDG 3 - Good Health and Well-being |
| topic |
angiogenesis endothelial cell hyperactivation ferroptosis lipid peroxidation oxidative stress polyurea dendrimers propranolol tumor vasculature stabilizers Oncology Cancer Research SDG 3 - Good Health and Well-being |
| description |
Funding: The project was funded by IPOLFG EPE and by iNOVA4Health (UID/Multi/04462/2019) a program financially supported by Fundação para a Ciência e Tecnologia (FCT)/Ministério da Educação e Ciência, through national funds. We also acknowledge funding from FCT-MCTES through the project DREAM—PTDC/MEC-ONC/29327/2017. FL-C PhD fellowship was funded by FCT (PD/BD/128337/2017). |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021-06-18T22:25:53Z 2021-05-10 2021-05-10T00:00:00Z |
| 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 |
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http://hdl.handle.net/10362/119581 |
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http://hdl.handle.net/10362/119581 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
2234-943X PURE: 31841566 https://doi.org/10.3389/fonc.2021.656229 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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