Inhibition of bioenergetic metabolism by the combination of metformin and 2-deoxyglucose highly decreases viability of feline mammary carcinoma cells

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...

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Bibliographic Details
Published in:Research in veterinary science 2017-10, Vol.114, p.461-468
Main Authors: Arbe, María Florencia, Fondello, Chiara, Agnetti, Lucrecia, Álvarez, Gabriel Martín, Tellado, Matías Nicolás, Glikin, Gerardo Claudio, Finocchiaro, Liliana María Elena, Villaverde, Marcela Solange
Format: Article
Language:English
Subjects:
2-Deoxyglucose
Animals
Antidiabetics
Antineoplastic Agents - pharmacology
Apoptosis
Autophagy
Bioenergetics
Breast cancer
Cancer
Cancer therapies
Carcinoma
Cats
Cell culture
Cell cycle
Cell Line, Tumor - metabolism
Cell Survival - drug effects
Deoxyglucose
Deoxyglucose - metabolism
Diabetes
Diabetes mellitus
Drugs
Energy Metabolism - drug effects
ErbB-2 protein
Feline mammary carcinoma cells
Flow cytometry
Hexokinase
Kinases
Lactic acid
Mammary gland
Mammary Neoplasms, Animal - metabolism
Metabolism
Metformin
Metformin - pharmacology
Modulation
Oxidants
Oxidizing agents
Phosphatase
ROS
Studies
Tumors
Veterinary medicine
Viability
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Summary: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 Ki6715%). 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 6.32mM, 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. •Metformin and 2-deoxyglucose synergize to kill feline mammary carcinoma cells.•The effectiveness depends on autophagy and oxidative stress.•2-Deoxyglucose prevents metformin-induced lactate increased.
ISSN:0034-5288
1532-2661
DOI:10.1016/j.rvsc.2017.07.035