Metformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2016 |
| Outros Autores: | , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da UFMG |
| Texto Completo: | https://doi.org/10.18632/oncotarget.10842 http://hdl.handle.net/1843/44534 |
Resumo: | CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico |
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2022-08-24T15:40:28Z2022-08-24T15:40:28Z2016-07-267345505755068https://doi.org/10.18632/oncotarget.108421949-2553http://hdl.handle.net/1843/44534CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorBackground: metformin is a biguanide, belonging to the oral hypoglycemic agents and is a widely used in the treatment of type 2 diabetes. Evidence indicate that Metformin inhibits cell proliferation in several human cancers and inhibits the Warburg phenomenon in tumor cells. Results: low PDH levels were observed in OSCC, and Metformin promotes an increase in PDH levels in hypoxic conditions. Metformin also reduced HIF-1α mRNA and protein levels. Metformin demonstrated antiproliferative effects, inhibited migration, increased the number of apoptotic cells and increased the transcription of caspase 3. Objective: the present study aims to explore the effects of Metformin in hypoxic conditions. Specifically, we focused on pyruvate dehydrogenase (PDH), (hypoxia-inducible factor 1α) HIF-1α levels and the oral squamous cell carcinoma (OSCC) cell phenotype. Additionally, we also investigated a theoretical consequence of Metformin treatment. Methods: PDH levels in patients with OSCC and oral dysplasia were evaluated. Metformin was administered in vitro to test the effect of Metformin under hypoxic conditions. The results were complemented by Bioinformatics analyses. Conclusions: in conclusion, our current findings show that Metformin reduces HIF-1α gene expression and increases PDH expression. Metformin inhibits cell proliferation and migration in the OSCC cell line model. Additionally, Metformin enhances the number of apoptotic cells and caspase 3 levels. Interestingly enough, Metformin did not increase the mutant p53 levels under hypoxic conditions.engUniversidade Federal de Minas GeraisUFMGBrasilICA - INSTITUTO DE CIÊNCIAS AGRÁRIASOncotargetBoca - CâncerCarcinoma de células escamosasMetformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinomainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.oncotarget.com/article/10842/text/Talita Antunes GuimarãesLucyana Conceição FariasEliane Macedo Sobrinho SantosCarlos Alberto de Carvalho FragaLissur Azevedo OrsiniLeandro de Freitas TelesJohn David FeltenbergerSabrina Ferreira de JesusMarcela Gonçalves de SouzaSérgio Henrique Sousa SantosAlfredo Maurício Batista de PaulaRicardo Santiago GomezAndré Luiz Sena Guimarãesinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/44534/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALMetformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma.pdfMetformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma.pdfapplication/pdf2334402https://repositorio.ufmg.br/bitstream/1843/44534/2/Metformin%20increases%20PDH%20and%20suppresses%20HIF-1%ce%b1%20under%20hypoxic%20conditions%20and%20induces%20cell%20death%20in%20oral%20squamous%20cell%20carcinoma.pdfddbe4d299199fe4b51a93b399260f97dMD521843/445342022-08-24 12:40:28.487oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2022-08-24T15:40:28Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
| dc.title.pt_BR.fl_str_mv |
Metformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma |
| title |
Metformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma |
| spellingShingle |
Metformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma Talita Antunes Guimarães Boca - Câncer Carcinoma de células escamosas |
| title_short |
Metformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma |
| title_full |
Metformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma |
| title_fullStr |
Metformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma |
| title_full_unstemmed |
Metformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma |
| title_sort |
Metformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma |
| author |
Talita Antunes Guimarães |
| author_facet |
Talita Antunes Guimarães Lucyana Conceição Farias Eliane Macedo Sobrinho Santos Carlos Alberto de Carvalho Fraga Lissur Azevedo Orsini Leandro de Freitas Teles John David Feltenberger Sabrina Ferreira de Jesus Marcela Gonçalves de Souza Sérgio Henrique Sousa Santos Alfredo Maurício Batista de Paula Ricardo Santiago Gomez André Luiz Sena Guimarães |
| author_role |
author |
| author2 |
Lucyana Conceição Farias Eliane Macedo Sobrinho Santos Carlos Alberto de Carvalho Fraga Lissur Azevedo Orsini Leandro de Freitas Teles John David Feltenberger Sabrina Ferreira de Jesus Marcela Gonçalves de Souza Sérgio Henrique Sousa Santos Alfredo Maurício Batista de Paula Ricardo Santiago Gomez André Luiz Sena Guimarães |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Talita Antunes Guimarães Lucyana Conceição Farias Eliane Macedo Sobrinho Santos Carlos Alberto de Carvalho Fraga Lissur Azevedo Orsini Leandro de Freitas Teles John David Feltenberger Sabrina Ferreira de Jesus Marcela Gonçalves de Souza Sérgio Henrique Sousa Santos Alfredo Maurício Batista de Paula Ricardo Santiago Gomez André Luiz Sena Guimarães |
| dc.subject.other.pt_BR.fl_str_mv |
Boca - Câncer Carcinoma de células escamosas |
| topic |
Boca - Câncer Carcinoma de células escamosas |
| description |
CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico |
| publishDate |
2016 |
| dc.date.issued.fl_str_mv |
2016-07-26 |
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2022-08-24T15:40:28Z |
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2022-08-24T15:40:28Z |
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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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http://hdl.handle.net/1843/44534 |
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https://doi.org/10.18632/oncotarget.10842 |
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1949-2553 |
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https://doi.org/10.18632/oncotarget.10842 http://hdl.handle.net/1843/44534 |
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eng |
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Oncotarget |
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Universidade Federal de Minas Gerais |
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UFMG |
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Brasil |
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ICA - INSTITUTO DE CIÊNCIAS AGRÁRIAS |
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Universidade Federal de Minas Gerais |
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