CONICET | Buscador de Institutos y Recursos Humanos

In recent years, there has been a growing interest in the biological activities of plants essential oils. Origanum vulgare L. species, belongs to the Lamiaceae family and is distributed in Europe, Mediterranean Basin and Asia and are mainly used for gastronomic purposes. The objective of this study was to evaluate the anti-melanoma action of Oreganum vulgare essential oils (OvEO) and the major terpenes that derive from it. In order to investigate the potential anticancer effects of OvEO in vivo, mice were injected subcutaneously with 1 × 106 viable melanoma B16 cells in the right flank. At 11 day, the mice were treated intratumorally with 5% OvEO in isotonic saline solution. OvEO inhibited tumor growth showing a reduction of 35-40% for tumor size on days 15, 17 and 19, which revealed a significant anti-melanoma potential. Then, we analysed the chemical composition of OvEO by gas chromatography and γ-terpinene (13.7%) and terpinen-4-ol (11.2%) were the main compounds. In vitro antiproliferative activity of these terpenes was assayed on culture of A375 and Lu1205, BRAF V600E mutant melanoma cells, by MTT assay. Terpinen-4-ol showed anti-proliferative properties at 0,05% concentration and induced death rate between 50-60% at concentrations of 0,1% on the several melanoma cells tested but did not decrease the exacerbated pERK1/2 levels on these cells. On the contrary, γ-terpinene did not show activity at these concentrations. On the other hand, the co-treatment with 0,05% Terpinen-4-ol increased the BRAF inhibition-induced cell death of Vemurafenib (Vf). Moreover, this terpene diminished the viability of A375 and Lu1205 Vf-resistant cells, which indicated that Terpinen-4-ol could improve the treatment of these types of melanomas that do not respond to therapy with BRAF inhibitors. Altogether, these results suggest that OvEO has anti-tumor activity and Terpinen-4-ol could be an important active principle of this essential oil to induce the death of tumor cells.