Secondary metabolites (essential oils) from sand-dune plants induce cytotoxic effects in cancer cells.

Despite advances in modern therapeutic strategies, cancer remains the second leading cause of death worldwide. Therefore, there is a constant need to develop more efficient anticancer targeting strategies. The anticancer therapeutic proprieties of medicinal plants and their bioactive compounds have been reported for several years, making natural extracts and/or compounds derived from these a promising source of novel anticancer agents. Sand dune plants are subjected to severe environmental stresses, leading to the development of adaptations, including the production of secondary metabolites with a wide range of bioactivities, such as: anti-inflammatory, analgesic, antiseptic, hypoglycaemic, hypotensive, antinociceptive, antioxidant and anticancer.The anticancer potential of sand dune plants remains under-investigated, so this research describes the characterisation of the composition of bioactive EOs from sand-dune plants of Peniche (Portugal), and assessment of their activity in vitro and potential mechanism of action.EOs were extracted from six sand-dune species of plants from Peniche sand dunes: Crithmum maritimum L., Seseli tortuosum L., Artemisia campestris subsp. maritima (DC.) Arcang., Juniperus phoenicea var. turbinata (Guss.) Parl., Otanthus maritimus (L.) Hoffmanns. & Link, and Eryngium maritimum L.. EOs composition was fully characterised chemically using Gas Chromatography-Mass Spectrometry (GC-MS). The assessment of anticancer activity and mechanism of action was performed in vitro using breast and colorectal cancer 2D and 3D spheroid cell line models, through cell proliferation assay, western blotting analysis, and cell cycle analysis.

EOs from the majority of the species tested (S. tortuosum, A. campestris subsp. maritima, O. maritimus, and E. maritimum) were mainly composed by hydrocarbon compounds (sequisterpenes and monoterpenes), showing antiproliferative activity in both 2D and 3D models. EO extracted from S. tortuosum and O. maritimus were identified as having the lowest IC₅₀ values for both cell lines when compared with the other species tested. Furthermore, this antiproliferative activity was associated with increased p21 expression and induction of apoptosis.

The present study suggests that EOs extracted from S. tortuosum and O. maritimus present promising cytotoxic properties. Further evaluation of the extracts and their key components as potential anticancer agents should therefore be explored.