Cancer cells shift their energy metabolism (ATP) production from Mitochondrial oxidative phosphorylation observed in non-tumour cells to cytosolic aerobic glycolysis. This change, known as the Warburg Effect, is mediated by increased expression of uncoupling protein-2 (UCP2), resulting in the uncoupling of oxidative phosphorylation of ATP in the mitochondria. It has been proposed that mitochondrial recoupling would be a novel therapeutic strategy for cancer. Oroxylin A has been observed to be an inhibitor of the uncoupling protein-2 (UCP2). This report details the synthesis of nanoparticles containing Oroxylin A encapsulated into PLGA, Solutol or nanofibrils. The effect of Oroxylin A alone and encapsulated Oroxylin A on the cell viability of mouse melanoma cells is studied, as well as the effect of Oroxylin A alone and encapsulated Oroxylin A on apoptosis (determined by caspase-9 activity). It was found that Oroxylin A alone had little effect on melanoma cell viability or apoptosis but that encapsulation of Oroxylin A into PLGA, Solutol or nanofibrils had a marked inhibitory effect on melanoma cell viability. Oroxylin A encapsulated into Solutol markedly stimulated caspase-9 while Oroxylin A encapsulated into PLGA strongly inhibited caspase-9 activity. The effect of PLGA or Solutol alone on melanoma, human colorectal carcinoma cells or human gastric adenocarcinoma cell viability was studied. PLGA showed little inhibition or was even, somewhat, stimulatory. Solutol, particularly at higher concentrations, was inhibitory.
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