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

Abstract

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. Aim of the study: 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. Materials and methods: 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. Results: 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 IC 50 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. Conclusions: 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.

Study of the Properties of In Vitro Dactylorhiza maculata (L.) Soó (Family Orchidaceae) Extracts

“…Currently, the number of studies on the use of medicinal plants in the treatment and prevention of a wide range of diseases in humans and animals has increased worldwide [ 5 ], including the development of feed additives, biologically active substances (BAS), that can replace antibiotics. This has to do with the fact that despite the effectiveness of antibiotics in treating and preventing livestock health problems, they also contribute to the development of adaptation to them in pathogenic microorganisms [ 6 ].…”

Spheroid-on-chip microfluidic technology for the evaluation of the impact of continuous flow on metastatic potential in cancer models in vitro

“… 42,43 MCF7 cells were selected as an alternative tumor type to validate on-chip which robustly forms spheroids. 44 Cells were cultured in high glucose DMEM (Dulbecco's Modified Eagle Medium) supplemented with 1% sodium pyruvate (Gibco), supplemented with 10% FBS (Gibco). Cells were maintained at 37 °C and 5% CO 2 in a humidified atmosphere.…”

“…Spheroids were formed and maintained as previously reported from either U-87 MG cells or MCF7 cells. 44,45 In short, cells were seeded in ultralow adherence (ULA), round bottom, 96-well plates at different cell densities, dependent on experiment (typically either 2.5 × 10 4 or 3.5 × 10 4 cells per well). Once the cell suspension was added to the microwells, the plate was left undisturbed for 96 h in a 37 °C, 5% CO 2 incubator to allow aggregation into spheroids.…”

PI3K inhibition as a novel therapeutic strategy for neoadjuvant chemoradiotherapy resistant oesophageal adenocarcinoma

“…Media was replaced every 2 days. Spheroids were imaged using the GelCount instrument (Oxford Optronix), and spheroid size determined as previously reported (19,20). Ambion pre-miR miRNA precursor molecules (Thermo Fisher Scientific, UK) were used for transient miR-187 overexpression.…”