Fig. 6

Schematic representation of the metabolic pathways altered by DFO administration and specific inhibitors. The iron chelator DFO is primarily taken up into cells by endocytosis. The chelation of iron inhibits PHD enzyme, leading to the accumulation of HIF1 α, thereby inducing a hypoxic response under normal oxygen conditions and increased production of lactate (final product of glycolysis). Overproduced lactate is excreted out of the cells by monocarboxylate transporter (MCT); however, suppression of this excretion process by CHC leads to accumulation of lactate in the cell. This increases the acidity inside the cell, which ultimately damages the cell