Loss of viability and impairment of the cell cycle by combining metabolic modulators in canine and feline melanoma cells

Abstract

Despite encouraging advances during the last decade, clinical management of malignant human, canine and feline melanoma continues to be a challenge. Thus, new therapeutic development is required. One of the hallmarks of cancer is metabolic rearrangement, including increased glucose metabolism. This metabolic alteration seems to be involved not only in cell proliferation but also in drug resistance, thus offering potential therapeutic targets. The aim of the present work was to investigate the in vitro effects of a combination of metformin (MET, an antidiabetic drug and OXPHOS inhibitor), 2-deoxyglucose (2DG, an HK inhibitor) and 6-aminonicotinamide (6AN, a G6PDH inhibitor) on two melanoma cell lines, Sc (canine) and Dc (feline) derived from spontaneous tumors. We found that both 2DG and MET treatment significantly decreased the cell viability of both cell lines (p < 0.05) in a concentration-dependent manner, whereas 6AN as monotherapy only significantly affected Sc. In addition, the effect of MET was significantly potentiated (p < 0.05) by the combination with both 2DG and 6AN in both cell lines. MET/2DG and MET/6AN significantly affected the cell cycle and increased the percentage of the subG0 population. These results support further studies to investigate the potential use of these metabolic drugs in a veterinary clinical setting.