info:eu-repo/semantics/article
Inhibition of bioenergetic metabolism by the combination of metformin and 2-deoxyglucose highly decreases viability of feline mammary carcinoma cells
Fecha
2017-10Registro en:
Arbe, María Florencia; Fondello, Chiara; Agnetti, Lucrecia; Alvarez, Gabriel Martín; Tellado, Matías Nicolás; et al.; Inhibition of bioenergetic metabolism by the combination of metformin and 2-deoxyglucose highly decreases viability of feline mammary carcinoma cells; Elsevier; Research in Veterinary Science; 114; 10-2017; 461-468
0034-5288
CONICET Digital
CONICET
Autor
Arbe, María Florencia
Fondello, Chiara
Agnetti, Lucrecia
Alvarez, Gabriel Martín
Tellado, Matías Nicolás
Glikin, Gerardo Claudio
Finocchiaro, Liliana Maria Elena
Villaverde, Marcela Solange
Resumen
Feline mammary carcinoma (FMC) is a highly aggressive pathology that has been proposed as an interesting model of breast cancer disease, especially for the hormone refractory subgroup. Recently, cancer cell metabolism has been described as a hallmark of cancer cells. Here, we investigate the effects and mechanism of metabolic modulation by metformin (MET, anti-diabetic drug), 2-deoxyglucose (2DG, hexokinase inhibitor) or a combination of both drugs, MET/2DG on two established FMC cells lines: AlRB (HER2 (3 +) and Ki67 < 5%) and AlRATN (HER2 (−) and Ki67 > 15%). We found that treatments significantly decreased both FMC cells viability by up to 80%. AlRB resulted more sensitive to 2DG than AlRATN (IC50: 3.15 vs 6.32 mM, respectively). The combination of MET/2DG potentiated the effects of the individually added drugs on FMC cells. In addition, MET/2DG caused an increased in intracellular oxidants, autophagic vesicles and completely inhibited colony formation.Conversely, only MET significantly altered plasma membrane integrity, presented late apoptotic/necrotic cells and increased both glucose consumption and lactate concentration. Our results support further studies to investigate the potential use of this metabolic modulation approach in a clinical veterinary setting.