Antiproliferative Activity of Olive Oil Phenolics against Human Melan oma Cells

Background: Virgin olive oil, the main source of lipids in a mediterranean diet, is broadly recognised to possess health-beneficial features, namely a protective role against cancer. It comprises several phenolic compounds, the major ones being tyrosol (p-hydroxyphenylethanol), hydroxytyrosol (3,4-dihydroxyphenylethanol), lignans and secoiridoids, namely oleuropein (OP) and the oleuropein aglycones 3,4-(dihydroxyphenyl) ethanol elenolic acid ester and 3,4-(dihydroxyphenyl)ethanol elenolic acid di-aldehyde. Objective: The goal of this work is the in vitro evaluation of the anti-proliferative activity against human amelanotic melanoma (C32 cell line) for hydroxytyrosol and the most important secoiridoids of olive oil. The effect of hydroxytyrosol on non-neoplastic cells (BJ fibroblass) was also investigated. Methods: Inhibition of cell proliferation was assessed by the Sulforhodamine colorimetric method, in both neoplastic and non-tumorigenic cells. Results: 3,4-(Dihydroxyphenyl)ethanol elenolic acid di-aldehyde and 3,4-(dihydroxyphenyl)ethanol elenolic acid ester secoiridoid aglycones were found to display growth-inhibiting activity (at ca. 100 μM), as opposed to oleuropein that elicited a strong protective effect at all concentrations (100 to 1000 μM). 3,4-Dihydroxyphenylethanol evidenced a dual effect (strongly dose-dependent) - cytoprotective for lower dosages and cytotoxic at high concentrations. Conclusion: Attending to the recognised structural dependence of the biological activity of phenolic derivatives, the previously gathered conformational data on the olive oil constituents presently investigated assisted the interpretation of their biological properties. This type of studies, coupling structural characterisation to biological assessment, allows the establishment of reliable structure activity relationships for polyphenolic compounds, ruling their cytoprotective vs cytotoxic activity and therefore their potential use as natural-based pharmacological agents.