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.

Our data suggests that WSB-1 may be an important regulator of aggressive metastatic disease in hormone receptor-negative breast cancer. WSB-1 could therefore represent a novel regulator and therapeutic target for secondary breast cancer in these patients.

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Abstract. Elevated expression of tissue factor (tF) has been associated with an increased risk of thrombosis in the majority of cancers. moreover, treatment of cancer patients with low molecular weight heparin (lmWh) appears to have beneficial effects that reach beyond controlling the immediate hypercoagulable state. in this study, we investigated the influence of the treatment of cancer cells with LMWH (0-2,000 µg/ml) on cell invasiveness and migration in cancer cell lines from five separate tissues; pancreatic, breast, colocarcinoma, ovarian and melanoma. the rate of cell invasion across collagen iV-coated membranes was suppressed in all cell lines tested on incubation with 2,000 µg/ml lmWh, but Bxpc-3 and mda-mB-231 cells also responded to the lowest concentration of 20 µg/ml lmWh. Furthermore, the rate of cell migration was reduced to varying extents in all of the cell lines tested on incubation with 20 µg/ml or higher concentrations of lmWh. the decrease in the rates of invasion and migration also strongly correlated with the reduction in tF protein expression and tF activity in these cells following incubation with lmWh. moreover, the lmWh-mediated decreases in cellular invasion in the most affected cell lines (Bxpc-3 and mda-mB-231) were restored by transfection of the cells with the mammalian pcmV-xl5-tF expression vector allowing independent overexpression of tF. in conclusion, lmWh appears to suppress the rate of cancer cell invasion and migration in vitro, through a mechanism that is at least in part dependent on the tF protein expression and activity in cancer cells. Introductionthe association between increased tissue factor (tF) expression and aggressiveness of cancer is well established. the expression of tF has been correlated with the histological grade of tumours (1), and the up-regulation of tF expression in cancer cells occurs early during the disease (2). Furthermore, the ability of tF to induce cellular cancer cell proliferation, migration and invasion has been documented (3-7). heparin treatment of cancer patients has been used as a means of controlling the risk of thrombotic episodes (8), and low molecular weight heparin (lmWh) has been reported to be suitable for the regulation of the procoagulant action of tF (9). there is data that incubation of cancer cell lines with lmWh results in the suppression of tF expression. additionally, we previously reported a reduction in the levels of circulating tF in the plasma from pancreatic cancer patients receiving prophylactic lmWh (daltaparin), compared to those not receiving the treatment (10). in this study, we further demonstrated the ability of lmWh to reduce the level of tF antigen and activity in cell lines from five separate tissues; BxPC-3 (pancreatic cancer), mda-mB-231 (breast cancer), loVo (colorectal cancer), SKOV-3 (ovarian cancer) and a375 (melanoma). crucially, we report that the incubation of these cancer cell lines with lmWh (20-2,000 µg/ml) reduces cellular invasion and migration through a tF-mediated mechanism in vitro. Material...