Cysteine allows ovarian cancer cells to adapt to hypoxia and to escape from carboplatin cytotoxicity
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| 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/10362/41058 |
Resumo: | The authors would like to acknowledge the Instituto Portugues de Oncologia de Lisboa Francisco Gentil (IPOLFG) for partially funding the project. We would also like to acknowledge Dr Dialina Brilhante and Dr. Teresa Guerreiro (Servico de Imuno-hemoterapia, IPOLFG) for providing blood donors samples; to Dr Humberto Goncalves (Pharmacy, IPOLFG) for paclitaxel and carboplatin preparation, and Marta Teixeira (IBET) for the technical support in 3D models. The study was also funded by Projecto TVI. This research was supported by Fundacao para a Ciencia e Tecnologia (FCT) (PhD ProRegeM program, PD/BD/105893/2014, FCT fellowship, PD/BD/105768/2014). iNOVA4Health - UID/Multi/04462/2013, a program financially supported by Fundacao para a Ciencia e Tecnologia/Ministerio da Educacao e Ciencia, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement is acknowledged. |
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Cysteine allows ovarian cancer cells to adapt to hypoxia and to escape from carboplatin cytotoxicitySDG 3 - Good Health and Well-beingThe authors would like to acknowledge the Instituto Portugues de Oncologia de Lisboa Francisco Gentil (IPOLFG) for partially funding the project. We would also like to acknowledge Dr Dialina Brilhante and Dr. Teresa Guerreiro (Servico de Imuno-hemoterapia, IPOLFG) for providing blood donors samples; to Dr Humberto Goncalves (Pharmacy, IPOLFG) for paclitaxel and carboplatin preparation, and Marta Teixeira (IBET) for the technical support in 3D models. The study was also funded by Projecto TVI. This research was supported by Fundacao para a Ciencia e Tecnologia (FCT) (PhD ProRegeM program, PD/BD/105893/2014, FCT fellowship, PD/BD/105768/2014). iNOVA4Health - UID/Multi/04462/2013, a program financially supported by Fundacao para a Ciencia e Tecnologia/Ministerio da Educacao e Ciencia, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement is acknowledged.Ovarian cancer is the second most common gynaecologic malignancy and the main cause of death from gynaecologic cancer, due to late diagnosis and chemoresistance. Studies have reported the role of cysteine in cancer, by contributing for hydrogen sulphide (H2S) generation and as a precursor of glutathione (GSH). However, the role of cysteine in the adaptation to hypoxia and therapy response remains unclear. We used several ovarian cancer cell lines, ES2, OVCAR3, OVCAR8, A2780 and A2780cisR, to clarify cysteine relevance in ovarian cancer cells survival upon hypoxia and carboplatin. Results show that ES2 and OVCAR8 cells presented a stronger dependence on cysteine availability upon hypoxia and carboplatin exposure than OVCAR3 cells. Interestingly, the A2780 cisR, but not A2780 parental cells, benefits from cysteine upon carboplatin exposure, showing that cysteine is crucial for chemoresistance. Moreover, GSH degradation and subsequent cysteine recycling pathway is associated with ovarian cancer as seen in peripheral blood serum from patients. Higher levels of total free cysteine (Cys) and homocysteine (HCys) were found in ovarian cancer patients in comparison with benign tumours and lower levels of GSH were found in ovarian neoplasms patients in comparison with healthy individuals. Importantly, the total and S-Homocysteinylated levels distinguished blood donors from patients with neoplasms as well as patients with benign from patients with malignant tumours. The levels of S-cysteinylated proteins distinguish blood donors from patients with neoplasms and the free levels of Cys in serum distinguish blood from patients with benign tumours from patients with malignant tumours. Herein we disclosed that cysteine contributes for a worse disease prognosis, allowing faster adaptation to hypoxia and protecting cells from carboplatin. The measurement of serum cysteine levels can be an effective tool for early diagnosis, for outcome prediction and follow up of disease progression.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)Instituto de Tecnologia Química e Biológica António Xavier (ITQB)RUNNunes, Sofia C.Ramos, CristianoLopes-Coelho, FilipaSequeira, Catarina OSilva, FernandaGouveia-Fernandes, SofiaRodrigues, ArmandaGuimarães, AntónioSilveira, MargaridaSanto, Vítor EAbreu, SofiaBrito, CatarinaFélix, AnaPereira, Sofia ASerpa, Jacinta2018-07-06T22:10:49Z2018-06-222018-06-22T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/41058eng2045-2322PURE: 4442602https://doi.org/10.1038/s41598-018-27753-yinfo: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:RCAAP2024-03-11T04:22:14Zoai:run.unl.pt:10362/41058Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:31:19.394657Repositório 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 |
Cysteine allows ovarian cancer cells to adapt to hypoxia and to escape from carboplatin cytotoxicity |
| title |
Cysteine allows ovarian cancer cells to adapt to hypoxia and to escape from carboplatin cytotoxicity |
| spellingShingle |
Cysteine allows ovarian cancer cells to adapt to hypoxia and to escape from carboplatin cytotoxicity Nunes, Sofia C. SDG 3 - Good Health and Well-being |
| title_short |
Cysteine allows ovarian cancer cells to adapt to hypoxia and to escape from carboplatin cytotoxicity |
| title_full |
Cysteine allows ovarian cancer cells to adapt to hypoxia and to escape from carboplatin cytotoxicity |
| title_fullStr |
Cysteine allows ovarian cancer cells to adapt to hypoxia and to escape from carboplatin cytotoxicity |
| title_full_unstemmed |
Cysteine allows ovarian cancer cells to adapt to hypoxia and to escape from carboplatin cytotoxicity |
| title_sort |
Cysteine allows ovarian cancer cells to adapt to hypoxia and to escape from carboplatin cytotoxicity |
| author |
Nunes, Sofia C. |
| author_facet |
Nunes, Sofia C. Ramos, Cristiano Lopes-Coelho, Filipa Sequeira, Catarina O Silva, Fernanda Gouveia-Fernandes, Sofia Rodrigues, Armanda Guimarães, António Silveira, Margarida Santo, Vítor E Abreu, Sofia Brito, Catarina Félix, Ana Pereira, Sofia A Serpa, Jacinta |
| author_role |
author |
| author2 |
Ramos, Cristiano Lopes-Coelho, Filipa Sequeira, Catarina O Silva, Fernanda Gouveia-Fernandes, Sofia Rodrigues, Armanda Guimarães, António Silveira, Margarida Santo, Vítor E Abreu, Sofia Brito, Catarina Félix, Ana Pereira, Sofia A Serpa, Jacinta |
| author2_role |
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) Centro de Estudos de Doenças Crónicas (CEDOC) Instituto de Tecnologia Química e Biológica António Xavier (ITQB) RUN |
| dc.contributor.author.fl_str_mv |
Nunes, Sofia C. Ramos, Cristiano Lopes-Coelho, Filipa Sequeira, Catarina O Silva, Fernanda Gouveia-Fernandes, Sofia Rodrigues, Armanda Guimarães, António Silveira, Margarida Santo, Vítor E Abreu, Sofia Brito, Catarina Félix, Ana Pereira, Sofia A Serpa, Jacinta |
| dc.subject.por.fl_str_mv |
SDG 3 - Good Health and Well-being |
| topic |
SDG 3 - Good Health and Well-being |
| description |
The authors would like to acknowledge the Instituto Portugues de Oncologia de Lisboa Francisco Gentil (IPOLFG) for partially funding the project. We would also like to acknowledge Dr Dialina Brilhante and Dr. Teresa Guerreiro (Servico de Imuno-hemoterapia, IPOLFG) for providing blood donors samples; to Dr Humberto Goncalves (Pharmacy, IPOLFG) for paclitaxel and carboplatin preparation, and Marta Teixeira (IBET) for the technical support in 3D models. The study was also funded by Projecto TVI. This research was supported by Fundacao para a Ciencia e Tecnologia (FCT) (PhD ProRegeM program, PD/BD/105893/2014, FCT fellowship, PD/BD/105768/2014). iNOVA4Health - UID/Multi/04462/2013, a program financially supported by Fundacao para a Ciencia e Tecnologia/Ministerio da Educacao e Ciencia, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement is acknowledged. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018-07-06T22:10:49Z 2018-06-22 2018-06-22T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/41058 |
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http://hdl.handle.net/10362/41058 |
| dc.language.iso.fl_str_mv |
eng |
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eng |
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2045-2322 PURE: 4442602 https://doi.org/10.1038/s41598-018-27753-y |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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