GLUCOSE METABOLISM INHIBITORS POTENTIATE METFORMIN CYTOTOXICITY IN CANINE AND FELINE MELANOMA CELLS

PAN, MELISA; ARBE, MARÍA FLORENCIA; GLIKIN, GC.; FINOCCHIARO L.M.E; VILLAVERDE M. S.

Congreso; Reunion Anual SAIC2018; 2018

Cancer cells metabolism rely in an exacerbation of glycolysis which supports the malignant phenotype. Feline and canine melanomas are highly aggressive pathologies that have been proposed as an interesting model of human melanoma disease. The aim of the present work was to investigate the in vitro effects of a combination of metformin (MET, antidiabetic drug, OXPHOS inhibitor), 2-deoxyglucose (2DG, HK inhibitor) and 6-aminonicotinamide (6AN, G6PD inhibitor) on two melanoma cell lines, Sc (canine) and Dc (feline) derived from spontaneous tumors. Sc and Dc were grown as monolayers at a subconfluent cell density. After 24 h of culture, cells were treated with 0.5 or 1 mM 2DG, 1 or 2.5 mM MET and 10 or 25 µM 6AN or a combination of them. Concentration-response curve were also assessed. The antitumor effects of bioenergetic inhibition were evaluated by the acidic phosphatase assay (APH) 5 days after treatments. We found that both cells lines significantly decreased cell viability (p