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Effect of Glucose on GLUT1-Dependent Intracellular Ascorbate Accumulation and Viability of Thyroid Cancer Cells

Jóźwiak, Paweł, Krześlak, Anna, Wieczorek, Marek, Lipińska, Anna
Nutrition and cancer 2015 v.67 no.8 pp. 1335-1343
RNA interference, ascorbic acid, cytotoxicity, dehydroascorbic acid, glucose, glucose transporters, hyperglycemia, neoplasm cells, oxidation, plasma membrane, thyroid neoplasms, viability
Enhanced glucose requirement of cancer cells is associated with an increased glucose transport across plasma membrane that is mediated by a family of facilitated glucose transporter proteins, named GLUTs. GLUT1 is the main transporter in thyroid cancer cells. Glucose is the principal physiological substrate of GLUT1; however, it is also capable of transporting of oxidized form of vitamin C [i.e., dehydroascorbic acid (DHAA) which inside the cells is reduced to ascorbic acid (AA)]. The objective of this study was to determine the effect of normo-, hypo-, and hyperglycemia conditions on GLUT1-dependent intracellular ascorbate accumulation and viability of thyroid cancer cells. GLUT1 seems to be the main DHAA transporter in thyroid cancer cells because its knockdown by RNAi reduced DHAA accumulation by more than 80%. The results showed that in thyroid cancer cells high glucose inhibits both transport of AA and DHAA. Inhibition of vitamin C transport by glucose had a cytotoxic effect on the cells. However, stabilization of vitamin C in one of 2 forms (i.e., AA or DHAA) abolished this effect. These results suggest that cytotoxic effect is rather associated with extracellular accumulation of vitamin C and changes of its oxidation state than with intracellular level of ascorbate.