Abstract
The rate of glucose uptake dramatically increases in cancer cells even in the presence of oxygen and fully functioning mitochondria. Cancer cells produce ATP by glycolysis rather than oxidative phosphorylation under aerobic conditions, a process termed as the “Warburg effect.” In the present study, we treated canine melanoma cells with the glucose analog 2-deoxy-D-glucose (2-DG) and investigated its effect on cell growth. 2-DG attenuated cell growth in a time- and dose-dependent manner. Cell growth was also inhibited following treatment with the glucose transporter (GLUT) inhibitor WZB-117. The treatment of 2-DG and WZB-117 attenuated the glucose consumption, lactate secretion and glucose uptake of the cells. The mRNA expression of the subtypes of GLUT was examined and GLUT1 and GLUT3 were found to be expressed in melanoma cells. The growth, glucose consumption and lactate secretion of melanoma cells transfected with siRNAs of specific for GLUT1 and GLUT3 was suppressed. These findings suggest that glucose uptake via GLUT1 and GLUT3 plays a crucial role for the growth of canine melanoma cells.
Highlights
Glucose is a main source of energy and carbon for mammalian cells
We first examined the contribution of glucose metabolism to the growth of canine melanoma cells using 2-deoxy-D-glucose (2-DG), a synthetic glucose analog. 2-DG is frequently used as an inhibitor of glucose metabolism, including glycolysis [34,35,36,37,38,39]
We observed that the effect of 2-DG on the cellular viability, glucose consumption, lactate secretion and glucose uptake was conserved in several canine melanoma cell lines (S1, S2 and S5 Figs)
Summary
Glucose is a main source of energy and carbon for mammalian cells. It is taken up by the cells via glucose transporters (GLUTs) and metabolized to pyruvate in the cytosol via glycolysis. Glycolysis-derived pyruvate is predominantly imported into the mitochondrial matrix where it is oxidized to acetyl coenzyme A (CoA) by the pyruvate dehydrogenase complex. The glucose metabolism of cancer cells is different from that of normal cells. Most pyruvate is converted to lactate in the cytoplasm by the action of lactate dehydrogenase and is secreted. These alterations are evident even in the presence of oxygen to support
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