Metformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma

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dc.creatorTalita Antunes Guimarães
dc.creatorLucyana Conceição Farias
dc.creatorEliane Macedo Sobrinho Santos
dc.creatorCarlos Alberto de Carvalho Fraga
dc.creatorLissur Azevedo Orsini
dc.creatorLeandro de Freitas Teles
dc.creatorJohn David Feltenberger
dc.creatorSabrina Ferreira de Jesus
dc.creatorMarcela Gonçalves de Souza
dc.creatorSérgio Henrique Sousa Santos
dc.creatorAlfredo Maurício Batista de Paula
dc.creatorRicardo Santiago Gomez
dc.creatorAndré Luiz Sena Guimarães
dc.date.accessioned2022-08-24T15:40:28Z
dc.date.accessioned2025-09-09T00:31:50Z
dc.date.available2022-08-24T15:40:28Z
dc.date.issued2016-07-26
dc.description.sponsorshipCNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico
dc.description.sponsorshipFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas Gerais
dc.description.sponsorshipCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
dc.identifier.doihttps://doi.org/10.18632/oncotarget.10842
dc.identifier.issn1949-2553
dc.identifier.urihttps://hdl.handle.net/1843/44534
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofOncotarget
dc.rightsAcesso Aberto
dc.subjectBoca - Câncer
dc.subjectCarcinoma de células escamosas
dc.titleMetformin increases PDH and suppresses HIF-1α under hypoxic conditions and induces cell death in oral squamous cell carcinoma
dc.typeArtigo de periódico
local.citation.epage55068
local.citation.issue34
local.citation.spage55057
local.citation.volume7
local.description.resumoBackground: 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.
local.publisher.countryBrasil
local.publisher.departmentICA - INSTITUTO DE CIÊNCIAS AGRÁRIAS
local.publisher.initialsUFMG
local.url.externahttps://www.oncotarget.com/article/10842/text/

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