Cytotoxicity of 2-deoxy-D-glucose and its tetra-acetate ester in tumoral cell lines

Mouse Lewis lung carcinoma cells (3LL-HH), mouse leukemic cells (L1210), mouse melanoma cells (B16F1), rat gliosarcoma cells (9L), rat hybrid insulin-producing cells (BRIN-BD11) and human hepatocellular carcinoma cells (HepG2) were cultured for 8 to 96 h in the absence or presence of 2-deoxy-D-glucose or its tetra-acetate ester (45 mu M to 0.8 mM). The ester was more efficient than the unesterified glucose analog in decreasing the growth of the tumoral cells, as assessed by either the generation of formazan from 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide or direct cell counting. At high concentration (0.8 mM), the ester even decreased the cell number below its initial value. Even under these conditions, a partial restoration ol-cell growth was observed, however, when the cells were cultured in a control medium after having been exposed for 8 h to 2-deoxy-D-glucose tetraacetate. These findings indicate that such an ester acts as a powerful cytostatic and cytotoxic agent in several tumoral cell lines.