Leandro de Freitas Teles, Eliane Macedo Sobrinho Santos, Alfredo Maurício Batista de Paula, John David Feltenberger, Sabrina Ferreira de Jesus, Marcela Gonçalves de Souza, Lissur Azevedo Orsini, Lucyana Conceição Farias, Ricardo Santiago Gomez, Carlos Alberto de Carvalho Fraga, André Luiz Sena Guimarães, Talita Antunes Guimarães, and Sérgio Henrique Sousa Santos
// Talita Antunes Guimaraes 1 , Lucyana Conceicao Farias 1 , Eliane Sobrinho Santos 1, 5 , Carlos Alberto de Carvalho Fraga 6, 7 , Lissur Azevedo Orsini 2 , Leandro de Freitas Teles 1 , John David Feltenberger 3 , Sabrina Ferreira de Jesus 1 , Marcela Goncalves de Souza 1 , Sergio Henrique Sousa Santos 4 , Alfredo Mauricio Batista de Paula 1 , Ricardo Santiago Gomez 2, * Andre Luiz Sena Guimaraes 1, * 1 Department of Dentistry, Universidade Estadual de Montes Claros, Montes Claros, Minas Gerais, Brazil 2 Department of Clinical, Surgery and Oral Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil 3 Texas Tech University Health Science Center, Lubbock, TX, USA 4 Institute of Agricultural Sciences, Food Engineering College, Universidade Federal de Minas Gerais (UFMG), Montes Claros, Minas Gerais, Brazil 5 Instituto Federal de Educacao, Ciencia e Tecnologia do Norte de Minas Gerais (IFNMG), Aracuai, Minas Gerais, Brazil 6 Faculdades Integradas Pitagoras, Montes Claros, Minas Gerais, Brazil 7 Faculdades Unidas do Norte de Minas, Montes Claros, Minas Gerais, Brazil * These authors contributed equally to this work Correspondence to: Andre Luiz Sena Guimaraes, email: andreluizguimaraes@gmail.com Ricardo Santiago Gomez, email: rsgomez.ufmg@gmail.com Keywords: proliferation, oral cancer, metformin, PDH, LDH-A Received: March 21, 2016 Accepted: July 09, 2016 Published: July 26, 2016 ABSTRACT Background: 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.