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Res Vet Sci. 2017 Oct;114:461-468. doi: 10.1016/j.rvsc.2017.07.035. Epub 2017 Aug 3.

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

Author information

1
Unidad de Transferencia Genética, Instituto de Oncología Dr. Ángel Roffo, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma Buenos Aires, Argentina.
2
Cátedra de Química Biológica, Facultad de Veterinaria, Universidad de Buenos, Ciudad Autónoma de Buenos Aires, Argentina.
3
Unidad de Transferencia Genética, Instituto de Oncología Dr. Ángel Roffo, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma Buenos Aires, Argentina. Electronic address: gglikin@bg.fcen.uba.ar.

Abstract

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 6.32mM, 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.

KEYWORDS:

2-Deoxyglucose; Autophagy; Feline mammary carcinoma cells; Metformin; ROS

PMID:
28802138
DOI:
10.1016/j.rvsc.2017.07.035
[Indexed for MEDLINE]

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