This excluded lactate dehydrogenase, which was shown here to be unaffected by the NaB. In order to maintain a high rate of glycolysis, it is mandatory for the tumor cells to have access to a ready supply of glucose. In many types of cancers, glucose transport is performed by class 1, 3 and 4, which as a rule can be overexpressed in tumor cells. It has been suggested that GLUT 1 and GLUT 3 are regulated by activation of HIF-1a. In the present work we showed that NaB treatment, particularly at 10 mM, strongly inhibited the expression of GLUT 1 and increased GLUT 3 expression in H460 cells, a result which suggest that a compensatory mechanism for glucose uptake is taking place. GLUT 1 is present in a variety of tissues that sense and respond to fluctuations in blood glucose levels. Our results indicated that HDACi effects on GLUT and HK in H460 is similar to that of brain cells. In this context, Gould and Holfman suggested that under normal conditions the capacity of HK to phosphorylates glucose is considerably greater than the capacity of the glucose transport systems in brain cells. However, under conditions of either high glucose demand or hypoglycemia, the expression of GLUT 3 in the brain with a low Km for hexoses may be required as an ancillary transport Erlotinib EGFR/HER2 inhibitor system. Upon entering the cell after the GLUT 1 barrier, glucose is immediately phosphorylated and thus initiates the glycolytic pathway. In H460 cells, HK associated to the mitochondria was found to be overexpressed as a consequence of NaB treatment. The question remained as to which HK isoform responded to the HDACi. This question was addressed by real time PCR which revealed that isoform HK I was upregulated and HK II down regulated by NaB. Upregulation of HK I was rather surprising and raised some points for speculation. For example, how did this finding fit with the general NaB induced depression of glycolysis reflected by the diminished lactate efflux? This question could be answered, at least partially, by highlighting the results in Figure 4 that show clearly that NaB was able to stimulate the PF-04217903 abmole activity of G6PDH indicating that G6P produced by HK I could be 
diverted to the PPP. The fate of G6P as a substrate to G6PDH also explains why G6P did not feedback inhibit HK I activity. In addition, activation of the PPP would provide a salvage pathway for anabolic metabolites in parallel with NADPH formation as a co adjuvant for reductive synthesis. Admittedly, other enzymes of the glycolytic pathway that were not investigated in the present work might have played key roles in the overall effects produced by the HDACis. One such example is hexose phosphate isomerase which has been recently shown to play an important modulatory activity in glycolysis using kinetic models. Because HPI can directly affect both, G6P and fructose-6-phosphate concentrations, and simultaneously be subject to inhibition by fructose 1,6-bisphosphate and PPP intermediaries, its response to HDACis could perhaps explain some of the observations described here. These experiments are currently under way. If glutamine catabolism is representative of the status of mitochondria of H460 cells, one could conclude that as a whole the organelle seems to be fully functional. As a matter of fact, we observed that NaB stimulated mitochondrial metabolism of H460 cells by measuring several parameters which collectively could be summarized as an enhancement of O2 consumption associated to ATP synthesis.