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Medicinal and aromatic plants’ properties, still an interesting research area, are attributed to the presence of various specialized products that possess important pharmacological activities. In the present study, six medicinal/aromatic plants (Sideritis cypria, Origanum dubium, Melissa officinalis, Mentha piperita, Thymus capitatus, and Salvia fruticosa) were evaluated for their phytochemical and nutritive composition, as well as their biological activities, including antioxidant, antimicrobial, and cytotoxic properties. The results obtained indicate that M. piperita was rich in proteins and minerals such as N and Mg, while S. cypria accumulated more K, Na, P, and Ca. The highest content of phenols and flavonoids was observed in M. piperita, followed by O. dubium and T. capitatus, which eventually influenced their high antioxidant capacity. NMR screening revealed the presence of (i) triterpenoids and hydroxycinnamic acid derivatives in M. officinalis; (ii) terpenoids, flavonoids, and phenolic acid derivatives in S. fruticosa; (iii) flavonoids and phenolic acid derivatives in M. piperita; (iv) phenolic monoterpenes in O. dubium and T. capitatus; and (v) terpenoids, flavones, and phenylethanoid glycosides in S. cypria. The results of the antimicrobial activity showed that the tested samples overall had quite good antimicrobial potential. High antibacterial activity was found in O. dubium and T. capitatus, while O. dubium and S. cypria exhibited great antifungal activities. The studied species also had an important effect on the viability of female-derived and colon cancer cells. In particular, in colon cancer cells, the extracts from T. capitatus, M. officinalis, M. piperita, and S. fruticosa exhibited a stronger effect on cell viability in the more metastatic cell line at significantly lower concentrations, indicating an important therapeutic potential in targeting highly metastatic tumors. This finding is worth further investigation. The present study unveiled interesting phytochemical profiles and biological properties of the six medicinal/aromatic plants, which should be further explored, contributing to green chemistry and the possible creation of natural health products for humans’ health/nutrition and additives in cosmetics.

Midkine (MDK) is a multifunctional secreted protein that can act as a cytokine or growth factor regulating multiple signaling pathways and being implicated in fundamental cellular processes, such as survival, proliferation, and migration. Although its expression in normal adult tissues is barely detectable, MDK serum levels are found to be elevated in several types of cancer, including hepatocellular carcinoma (HCC). In this review, we summarize the findings of recent studies on the role of MDK in HCC diagnosis and progression. Overall, studies show that MDK is a powerful biomarker for HCC early diagnosis, as it can differentiate not only between HCC patients and normal individuals but also between HCC patients and patients with other liver pathologies. It is correlated with high recurrence rates and was shown to be valuable for the diagnosis of early-stage HCC, even in patients negative for α-fetoprotein (AFP), the most commonly used biomarker for HCC diagnosis. A comparison with AFP reveals that MDK is inferior to AFP with regard to specificity but significantly superior with regard to sensitivity, which further indicates the need for using both biomarkers for more effective HCC diagnosis.

As metastasis is responsible for most cancer-related deaths, understanding the cellular and molecular events that lead to cancer cell migration and invasion will certainly provide insights into novel anti-metastatic therapeutic targets. Fascin-1 is an actin-bundling protein fundamental to all physiological or pathological processes that require cell migration. It is responsible for cross-linking actin microfilaments during the formation of actin-rich cellular structures at the leading edge of migrating cells such as filopodia, lamellipodia and invadopodia. While most epithelial tissues express low levels of Fascin-1, it is dramatically elevated in the majority of cancers and its expression has been associated with more aggressive disease and decreased overall survival. Hence, it has been proposed as a potential anti-cancer target. In the present review, we studied recent literature with regard to Fascin-1 expression in different cancers, its role in altering the mechanical properties of cancer cells, promoting cancer cell migration, invasion and metastasis and the effect of its inhibition, via various pharmacological inhibitors, in eliminating metastasis in vitro and/or in vivo. Recent studies corroborate the notion that Fascin-1 is critically involved in metastasis and prove that it is a valuable anti-metastatic target that is worth investigating further.

Cell-extracellular matrix interactions, or focal adhesions (FA), are crucial for tissue homeostasis but are also implicated in cancer. Integrin-Linked Kinase (ILK) is an abundantly expressed FA protein involved in multiple signaling pathways. Here, we reviewed the current literature on the role of ILK in breast cancer (BC). Articles included in vitro and in vivo experiments as well as studies in human BC samples. ILK attenuation via silencing or pharmaceutical inhibition, leads to apoptosis or inhibition of epithelial-to-mesenchymal transition, and cell invasion whereas ILK overexpression suppresses anoikis and promotes tumor growth and metastasis. Finally, ILK is upregulated in BC tumors and its expression is associated with grade, and metastasis. Therefore, ILK should be evaluated as a potential anti-cancer pharmaceutical target.

As extracellular matrix (ECM) nano-characteristics play a crucial role in cell behavior, including cancer development and metastasis, several ECM in vitro models have been used in order to study cells behavior under different biochemical and mechanical conditions. Among the ECM constituents, collagen (especially collagen type I) has been extensively used as an essential component of ECM models, since it is one of the most abundant ECM protein. Use of three-dimensional (3D) collagen gels provides the advantage of allowing the cells to grow in a 3D environment that bears strong similarities to their natural, in vivo setting. Thus, the ability to form collagen gels with tunable stiffness and well defined naturally occurring nano-characteristics is crucial for these studies. Atomic Force Microscopy (AFM) is a unique tool that is ideal for the complete characterization of such models, in terms of morphology and mechanical properties without destroying the collagen fiber structure. In this protocol, the development and the AFM nano-scale characterization of 3D collagen type I gels is presented. The protocol includes: • The formation of 3D collagen type I gels with tunable stiffness • The preparation of histological sections from collagen gels • The AFM-based morphological and mechanical nano-characterization of the gels Method name: AFM for 3D collagen gels, Keywords: Collagen gel histological sections, D-band periodicity, Stiffness, Young’s modulus

Cancer is a multifactorial disease responsible for millions of deaths worldwide. It has a strong genetic background, as mutations in oncogenes or tumor suppressor genes contribute to the initiation of cancer development. Integrin signaling as well as the signaling pathway of Ras oncogene, have been long implicated both in carcinogenesis and disease progression. Moreover, they have been involved in the promotion of metastasis, which accounts for the majority of cancer-related deaths. Ras Suppressor-1 (RSU1) was identified as a suppressor of Ras-induced transformation and was shown to localize to cell-extracellular matrix adhesions. Recent findings indicate that its expression is elevated in various cancer types, while its role in regulating metastasis-related cellular processes remains largely unknown. Interestingly, there is no in vivo work in the field to date, and thus, all relevant knowledge stems from in vitro studies. In this review, we summarize recent studies using breast, liver and brain cancer cell lines and highlight the role of RSU1 in regulating cancer cell invasion.

Metastasis is a multistep process in which tumor extracellular matrix (ECM) and cancer cell cytoskeleton interactions are pivotal. ECM is connected, through integrins, to the cell’s adhesome at cell–ECM adhesion sites and through them to the actin cytoskeleton and various downstream signaling pathways that enable the cell to respond to external stimuli in a coordinated manner. Cues from cell-adhesion proteins are fundamental for defining the invasive potential of cancer cells, and many of these proteins have been proposed as potent targets for inhibiting cancer cell invasion and thus, metastasis. In addition, ECM accumulation is quite frequent within the tumor microenvironment leading in many cases to an intense fibrotic response, known as desmoplasia, and tumor stiffening. Stiffening is not only required for the tumor to be able to displace the host tissue and grow in size but also contributes to cell–ECM interactions and can promote cancer cell invasion to surrounding tissues. Here, we review the role of cell adhesion and matrix stiffness in cancer cell invasion and metastasis.

Recent studies have implied that osteoarthritis (OA) is a metabolic disease linked to deregulation of genes involved in lipid metabolism and cholesterol efflux. Sterol Regulatory Element Binding Proteins (SREBPs) are transcription factors regulating lipid metabolism with so far no association with OA. Our aim was to test the hypothesis that SREBP-2, a gene that plays a key role in cholesterol homeostasis, is crucially involved in OA pathogenesis and to identify possible mechanisms of action.We performed a genetic association analysis using a cohort of 1,410 Greek OA patients and healthy controls and found significant association between single nucleotide polymorphism (SNP) 1784G>C in SREBP-2 gene and OA development. Moreover, the above SNP was functionally active, as normal chondrocytes' transfection with SREBP-2-G/C plasmid resulted in interleukin-1β and metalloproteinase-13 (MMP-13) upregulation. We also evaluated SREBP-2, its target gene 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR), phospho-phosphoinositide3-kinase (PI3K), phospho-Akt, integrin-alphaV (ITGAV) and transforming growth factor-β (TGF-β) mRNA and protein expression levels in osteoarthritic and normal chondrocytes and found that they were all significantly elevated in OA chondrocytes. To test whether TGF-β alone can induce SREBP-2, we treated normal chondrocytes with TGF-β and found significant upregulation of SREBP-2, HMGCR, phospho-PI3K and MMP-13. We also showed that TGF-β activated aggrecan (ACAN) in chondrocytes only through Smad3, which interacts with SREBP-2. Finally, we examined the effect of an integrin inhibitor, cyclo-RGDFV peptide, on osteoarthritic chondrocytes, and found that it resulted in significant upregulation of ACAN and downregulation of SREBP-2, HMGCR, phospho-PI3K and MMP-13 expression levels.We demonstrated, for the first time, the association of SREBP-2 with OA pathogenesis and provided evidence on the molecular mechanism involved. We suggest that TGF-β induces SREBP-2 pathway activation through ITGAV and PI3K playing a key role in OA and that integrin blockage may be a potential molecular target for OA treatment.

Cell-cell junctions are essential for epithelial and endothelial tissue formation and communication between neighboring cells. We report here that migfilin, a recently identified component of cell-extracellular matrix adhesions, is recruited to cell-cell junctions in response to cadherin-mediated cell-cell adhesions. Migfilin is detected at cell-cell junctions in both epithelial and endothelial cells. It forms detergent-resistant, discrete clusters that associate with actin bundles bridging neighboring cells. Immunoelectron microscopic analyses reveal that migfilin is closely associated with β-catenin, but not desmosomes, at cell-cell junctions. Furthermore, we show that the C-terminal LIM domains, but not its N-terminal domain, mediates migfilin localization to cell-cell junctions. The site mediating the localization of migfilin to cell-cell junctions at least partially overlaps with that mediating the localization of migfilin to cell-ECM adhesions. Finally, siRNA-mediated depletion of migfilin compromised the organization of adherens junctions and weakened cell-cell association. These results identify migfilin as a component of adherens junctions and suggest an important role for migfilin in the organization of the cell-cell adhesion structure. [ABSTRACT FROM AUTHOR]