Glycolytic enzyme inhibitors affect pancreatic cancer survival by modulating its signaling and energetics.

ABSTRACT

BACKGROUND AND AIM: The importance of glycolysis in cancer cells is well documented. The effects of inhibiting glycolysis using metabolic inhibitors iodoacetate (IAA), an inhibitor of GAPDHase, and 3-bromopyruvate (3BP), an inhibitor of hexokinase-II, on survival and signaling of pancreatic cancer cells (Panc-1) were investigated. MATERIALS AND METHODS: Cellular survival was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Lactate dehydrogenase (LDH) assay was used to analyze the induced necrosis and protein levels were evaluated using Western blot analysis. RESULTS: The results show that the inhibitors lowered cellular survival and increased cellular necrosis. Mitogenic signaling pathways were affected by 3BP but not by IAA. CONCLUSION: We conclude that there may be a cross-talk between signaling pathways and glycolysis in regulating pancreatic cancer cell survival and signaling. Thus, a combination of agents that inhibit both energy production and cell signaling may provide a novel and effective approach to target pancreatic cancer effectively.