Oleuropein-enriched olive leaf extract affects BRAF melanoma cells metabolism

Previously we found that Oleuropein (Ole), the major constituent of olive leaves, affected several properties of A375 BRAF V600E mutant melanoma cells (1). As many cancers, A375 cells express a very high level of replication using glucose as energy substrate and are usually addicted to Warburg effect (2). The aim of this study was to investigate if an Ole-enriched olive leaf extract was able to inhibit melanoma cell glycolysis, metabolic attitude tight related to proliferation and motility. Treatment with 200 µM non toxic dose of Ole-enriched olive leaf extract for 24-48h inhibited the glycolytic activity of melanoma cells, evaluated using Agilent Seahorse XFe96 Analyzer, and this decrease was related to the reduction of many important glycolytic markers, in particular PKM2 (assessed through real time PCR and Western Blot analysis). The PKM2 is an isoform of pyruvate kinase muscle isozyme, usually up-regulated in cancer cells. Following the reduction of glycolysis, melanoma cells expressed also a significant decrease of cell proliferation and motility assessed by wound healing assay. In conclusion, Ole-enriched olive leaf extracts represent a potent natural product able to affect the metabolism of melanoma cells, a property that may be used in novel strategies of complementary therapy.