Abstract
Cancer cells shift their energy metabolism (ATP) production from Mitochon-drial oxidative phosphorylation observed in non-tumour cells to cytosolic aer-obic glycolysis. This change, known as the Warburg Effect, is mediated by increased expression of uncoupling protein-2 (UCP2), resulting in the uncou-pling 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 Orox-ylin A alone and encapsulated Oroxylin A on the cell viability of mouse mela-noma 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 adenocarci-noma cell viability was studied. PLGA showed little inhibition or was even, somewhat, stimulatory. Solutol, particularly at higher concentrations, was in-hibitory.