Anti-proliferative and pro-apoptotic effects of oleuropein and hydroxytyrosol in melanoma cells.

Metastatic melanoma is the most deadly form of skin cancer that arises from transformed melanocytes of the basal region of epidermis. Melanoma cells are resistant to a wide range of chemotherapeutic and radiotherapeutic treatments, therefore, there is an urgent need for new and efficient therapeutic agents. In this contest, we studied the olive oil components that have been shown to induce the death for apoptosis of several cancer cells mainly through its phenolic compounds. The three phenolic compounds in highest concentration in olive oil are the glycoside oleuropein, hydroxytyrosol (3,4-dihydroxyphenyl ethanol) and tyrosol. In this study we investigated the anti-proliferative and pro-apoptotic potentials of oleuropein, tyrosol and hydroxytyrosol in A375, HT144 and M74 human melanoma cell lines using proliferation assays (MTS assay), western blot and DeadEnd(TM) Colorimetric TUNEL assay. In particular, the MTS assays showed that 200 ?g of oleuropein and 250 ?g of hydroxytyrosol remarkably reduced cell viability of treated melanoma cells. However tyrosol does not affect melanoma cell viability. Moreover, the results reported suggest that oleuropein and hydroxytyrosol treatment induces the melanoma cells apoptosis through PARP inactivation, caspase 8 and caspase 9 activation as well as increasing expression of p53 and gH2AX. Furthermore oleuropein and hydroxytyrosol cell apoptosis was confirmed through TUNEL experiments. In conclusion, these data show that the main phenolic compounds of olive oil, hydroxytyrosol and oleuropein, have potential chemotherapeutic properties and might provide basis for the design of new therapeutic agents for effective treatment of this highly invasive tumour.