Na/K-ATPase as a target for anticancer drugs: studies with perillyl alcohol
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2015 |
| Outros Autores: | , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/11493 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. |
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Garcia, Diogo GomesFaria Neto, Hugo Caire de CastroSilva, Camila Ignácio daSouza, Kauê Francisco Correa de Souza eAlbuquerque, Cassiano Felippe Gonçalves deSilva, Adriana RibeiroAmorim, Lidia Maria da Fonte deFreire, Aline SoaresSantelli, Ricardo ErthalDiniz, Luan PereiraGomes, Flávia Carvalho AlcantaraFaria, Mauro Velho de CastroBurth, Patrícia2015-08-19T13:49:21Z2015-08-19T13:49:21Z2015GARCIA, Diogo Gomes; et al. Na/K-ATPase as a target for anticancer drugs: studies with perillyl alcohol. Molecular Cancer , v.14, n.105, 14p, 2015.1476-4598https://www.arca.fiocruz.br/handle/icict/1149310.1186/s12943-015-0374-5engBioMed CentralNa/K-ATPase as a target for anticancer drugs: studies with perillyl alcoholinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Niterói, RJ, Brasil.Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Niterói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Niterói, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Química. Departamento de Química Analítica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Química. Departamento de Química Analítica. Rio de Janeiro, RJ, BrasilUniversidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Rio de Janeiro, RJ, Brasil.Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas. Departamento de Medicina Interna. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Instituto de Biologia. Departamento de Biologia Celular e Molecular. Niterói, RJ, Brasil.Background: Na/K-ATPase (NKA) is inhibited by perillyl alcohol (POH), a monoterpene used in the treatment of tumors, including brain tumors. The NKA α1 subunit is known to be superexpressed in glioblastoma cells (GBM). This isoform is embedded in caveolar structures and is probably responsible for the signaling properties of NKA during apoptosis. In this work, we showed that POH acts in signaling cascades associated with NKA that control cell proliferation and/or cellular death. Methods: NKA activity was measured by the amount of non-radioactive Rb+ incorporation into cultured GBM cell lines (U87 and U251) and non-tumor cells (mouse astrocytes and VERO cells). Cell viability was measured by lactate dehydrogenase levels in the supernatants of POH-treated cells. Activated c-Jun N-terminal Kinase (JNK) and p38 were assessed by western blotting. Apoptosis was detected by flow cytometry and immunocytochemistry, and the release of interleukins was measured by ELISA. Results: All four cell types tested showed a similar sensitivity for POH. Perillic acid (PA), the main metabolite of POH, did not show any effect on these cells. Though the cell viability decreased in a dose-dependent manner when cells were treated with POH, the maximum cytotoxic effect of PA obtained was 30% at 4 mM. 1.5 mM POH activated p38 in U87 cells and JNK in both U87 and U251 cells as well as mouse astrocytes. Dasatinib (an inhibitor of the Src kinase family) and methyl β-cyclodextrin (which promotes cholesterol depletion in cell membranes) reduced the POH-induced activation of JNK1/2 in U87 cells, indicating that the NKA-Src complex participates in this mechanism. Inhibition of JNK1/2 by the JNK inhibitor V reduced the apoptosis of GBM cells that resulted from POH administration, indicating the involvement of JNK1/2 in programmed cell death. 1.5 mM POH increased the production of interleukin IL-8 in the U251 cell supernatant, which may indicate a possible strategy by which cells avoid the cytotoxic effects of POH. Conclusions: A signaling mechanism mediated by NKA may have an important role in the anti-tumor action of POH in GBM cells.Na/K-ATPasePerillyl alcoholJNKU87 and U251 glioma cellsProteínas Quinases JNK Ativadas por MitógenoNeoplasias Encefálicasinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1914https://www.arca.fiocruz.br/bitstream/icict/11493/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALdiogo_garcia_etal_IOC_2015.pdfapplication/pdf3737573https://www.arca.fiocruz.br/bitstream/icict/11493/2/diogo_garcia_etal_IOC_2015.pdf1b84623ec38ac4ed0b27482edd41330eMD52TEXTdiogo_garcia_etal_IOC_2015.pdf.txtdiogo_garcia_etal_IOC_2015.pdf.txtExtracted texttext/plain56069https://www.arca.fiocruz.br/bitstream/icict/11493/3/diogo_garcia_etal_IOC_2015.pdf.txt212dcbf1627fec0a5c866604de524fb5MD53icict/114932022-06-24 13:03:08.115oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352022-06-24T16:03:08Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
Na/K-ATPase as a target for anticancer drugs: studies with perillyl alcohol |
| title |
Na/K-ATPase as a target for anticancer drugs: studies with perillyl alcohol |
| spellingShingle |
Na/K-ATPase as a target for anticancer drugs: studies with perillyl alcohol Garcia, Diogo Gomes Na/K-ATPase Perillyl alcohol JNK U87 and U251 glioma cells Proteínas Quinases JNK Ativadas por Mitógeno Neoplasias Encefálicas |
| title_short |
Na/K-ATPase as a target for anticancer drugs: studies with perillyl alcohol |
| title_full |
Na/K-ATPase as a target for anticancer drugs: studies with perillyl alcohol |
| title_fullStr |
Na/K-ATPase as a target for anticancer drugs: studies with perillyl alcohol |
| title_full_unstemmed |
Na/K-ATPase as a target for anticancer drugs: studies with perillyl alcohol |
| title_sort |
Na/K-ATPase as a target for anticancer drugs: studies with perillyl alcohol |
| author |
Garcia, Diogo Gomes |
| author_facet |
Garcia, Diogo Gomes Faria Neto, Hugo Caire de Castro Silva, Camila Ignácio da Souza, Kauê Francisco Correa de Souza e Albuquerque, Cassiano Felippe Gonçalves de Silva, Adriana Ribeiro Amorim, Lidia Maria da Fonte de Freire, Aline Soares Santelli, Ricardo Erthal Diniz, Luan Pereira Gomes, Flávia Carvalho Alcantara Faria, Mauro Velho de Castro Burth, Patrícia |
| author_role |
author |
| author2 |
Faria Neto, Hugo Caire de Castro Silva, Camila Ignácio da Souza, Kauê Francisco Correa de Souza e Albuquerque, Cassiano Felippe Gonçalves de Silva, Adriana Ribeiro Amorim, Lidia Maria da Fonte de Freire, Aline Soares Santelli, Ricardo Erthal Diniz, Luan Pereira Gomes, Flávia Carvalho Alcantara Faria, Mauro Velho de Castro Burth, Patrícia |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Garcia, Diogo Gomes Faria Neto, Hugo Caire de Castro Silva, Camila Ignácio da Souza, Kauê Francisco Correa de Souza e Albuquerque, Cassiano Felippe Gonçalves de Silva, Adriana Ribeiro Amorim, Lidia Maria da Fonte de Freire, Aline Soares Santelli, Ricardo Erthal Diniz, Luan Pereira Gomes, Flávia Carvalho Alcantara Faria, Mauro Velho de Castro Burth, Patrícia |
| dc.subject.en.pt_BR.fl_str_mv |
Na/K-ATPase Perillyl alcohol JNK U87 and U251 glioma cells |
| topic |
Na/K-ATPase Perillyl alcohol JNK U87 and U251 glioma cells Proteínas Quinases JNK Ativadas por Mitógeno Neoplasias Encefálicas |
| dc.subject.decs.pt_BR.fl_str_mv |
Proteínas Quinases JNK Ativadas por Mitógeno Neoplasias Encefálicas |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. |
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2015 |
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2015-08-19T13:49:21Z |
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2015-08-19T13:49:21Z |
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2015 |
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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.citation.fl_str_mv |
GARCIA, Diogo Gomes; et al. Na/K-ATPase as a target for anticancer drugs: studies with perillyl alcohol. Molecular Cancer , v.14, n.105, 14p, 2015. |
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https://www.arca.fiocruz.br/handle/icict/11493 |
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1476-4598 |
| dc.identifier.doi.pt_BR.fl_str_mv |
10.1186/s12943-015-0374-5 |
| identifier_str_mv |
GARCIA, Diogo Gomes; et al. Na/K-ATPase as a target for anticancer drugs: studies with perillyl alcohol. Molecular Cancer , v.14, n.105, 14p, 2015. 1476-4598 10.1186/s12943-015-0374-5 |
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BioMed Central |
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BioMed Central |
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