Search

Crocus sativus L. (saffron), was applied as a spice, food colorant and medicine since four millennia ago and has been used as a remedy for various maladies. In the last three decades, the anti-primary tumor properties of saffron and its main carotenoids, crocin and crocetin, have been well explored. Despite the fact that metastasis is the leading cause of death in cancer patients, the anti-metastatic potential of saffron and its carotenoids has been surveyed only this decade. This review aims to provide an unprecedented overview of the anti-metastatic effects of saffron, crocin and crocetin, and the mechanisms underlying these effects. Investigations on various cancers demonstrated the anti-migratory, anti-invasion, anti-angiogenic potentials of saffron and its carotenoids, as well as their effects suppressing cell-ECM adhesion and enhancing cell-cell attachment. Saffron and its carotenoids exert their impact through different mechanisms such as reduction of CD34 and suppression of Wnt/β-catenin, Ras/ERK, P38, DCLK1, EMT, matrix metalloproteinases and urokinases. Crocin displayed more effective anti-metastatic potency, in comparison with saffron extract and crocetin. The bioaccessibility/bioavailability, nontoxicity on normal cells, confirmed anti-tumor efficiency and the recent evidence on the anti-metastatic potential of saffron and its carotenoids, recommends them as a propitious multipotent dietary agent and herbal medicine.

2-hydroxy-6-tridecylbenzoic acid is alkylsalicylic acid monomer compound, abundantly existed in the ginkgo biloba extracts, however, the underlying mechanism of its anti-migration and anti-invasion effects in triple-negative breast cancer (TNBC) is not clear. Here, 2-hydroxy-6 -tridecylbenzoic acid inhibited MDA-MB-231 and 4 T-1 cells growth without toxicity to MCF-10A normal breast cells. Meanwhile, 2-hydroxy-6-tridecylbenzoic acid inhibited cells migration and invasion as well as EMT with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, Vimentin, Snail, MMP-2 and MMP-9 expression. The inhibition was further demonstrated by the enhancement of cytochrome P450 (CYP) 1B1 expression through the activation of AMP activated protein kinase (AMPK) in MDA-MB-231 and 4 T-1 cells. Silencing of CYP1B1 and AMPK with siRNA blocked the inhibitory effects of migration and invasion, and reversed the EMT related genes. These findings may provide a novel mechanism of the 2-hydroxy-6-tridecylbenzoic acid as a molecular-targeted therapeutic drug for TNBC patients.

The anti-invasion defences of the Second World War are still a prominent part of the modern landscape (Barclay 2013). The defences built during the First World War are, however, less well known. Some of these, indeed, have been misidentified as having been built in the later war, and many places were defended in both conflicts. Even less well known are the defences planned, and in some cases built, between 1900 and 1914, as set out in the Army’s ‘Defence Schemes’ for Scotland, and in the records of individual coast defence batteries. This paper sets out the plans to defend two adjacent parts of Scotland between 1900 and 1919, the coasts of the Tay and Forth estuaries, in the wider context of the defence of the UK.

The studies described in this thesis have investigated the anti-inflammatory effects and possible mechanisms of non-digestible oligosaccharides (NDOs), including galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS), in respiratory infections in calves naturally exposed to respiratory pathogens, with a possible translation to human respiratory infections. An in vivo model in calves and in vitro models in primary bronchial epithelial cells obtained from calves and human lung epithelial cells were used to investigate the potential effects and mechanisms of GOS and FOS. Anti-inflammatory effects of GOS and FOS observed in vitro were compared with the effects on inflammatory markers in the airway and blood of calves fed with these NDOs. The main mechanisms related to anti-inflammatory effects of GOS and FOS derived from the present in vitro studies include 1) the anti-bacterial effect of GOS at high concentrations on respiratory pathogens (e.g., Mannheimia haemolytica and Mycoplasma pneumoniae), 2) possible interference with Toll-like receptor 4 proinflammatory signaling and inhibition of oxidative stress by GOS at low concentrations, and 3) possible interference with Toll-like receptor 5 proinflammatory signaling and protection of airway epithelial barrier function by FOS. Due to these mechanisms, (oral or intranasal) GOS and FOS (partly) relieved lung infections and suppressed airway and systemic inflammation in calves. Finally, these results might contribute to reducing the future use of antibiotics in livestock species and humans and need to be incorporated into the evolving knowledge of microbiota-dependent or -independent effects of NDOs.

When primary cancer faces limited oxygen and nutrient supply, it undergoes an epithelial-mesenchymal transition, which increases cancer cell motility and invasiveness. The migratory and invasive cancer cells often exert aggressive cancer development or even cancer metastasis. In this study, we investigated a novel compound, 3-acetyl-5,8-dichloro-2-((2,4-dichlorophenyl)amino)quinolin-4(1H)-one (ADQ), that showed significant suppression of wound healing and cellular invasion. This compound also inhibited anchorage-independent cell growth, multicellular tumor spheroid survival/invasion, and metalloprotease activities. The anti-proliferative effects of ADQ were mediated by inhibition of the Akt pathway. In addition, ADQ reduced the expression of mesenchymal markers of cancer cells, which was associated with the suppressed expression of Twist1. In conclusion, ADQ successfully suppressed carcinogenic activity by inhibiting the Akt signaling pathway and Twist1, which suggests that ADQ may be an efficient candidate for cancer drug development.

Aims and background Although glioblastomas infiltrate diffusely into adjacent brain, it is difficult to unequivocally identify the solitary invading glioma cell. It is necessary to develop coculture models to study the motility of glioma cells, and to monitor the cellular morphology, movement direction, migration area and invasion rate. Methods Cerebral slices were cultured on Millicell-CM membrane inserts in a petri dish. The neuronal viability and organizational structure of the brain sections were well maintained by experimental verification. C6 cell clones with persistent enhanced green fluorescent protein (EGFP) expression were established. EGFP-expressing glioma cells were cultured to form aggregates, which were implanted on the brain slices. The invasion area and migration rates of C6 cells on brain slices were measured. We evaluated the invasion area and depth after C6 cells were treated with the Rac1 inhibitor NSC23766. Results We successfully established the glioma cell-brain slice coculture model. In coculture, the average migration rate of C6 glioma cells within brain slices reached 11.36-15.27 urn/hour. The polarity of C6 glioma cells was parallel to the white matter tracts after 7 days. The invasive ability of C6 cells (depth: 105.3 ± 10.3 μm) treated with NSC23766 was weakened compared with the control group (depth: 198 ± 9.2 μm) within the white matter of brain slices (t = 16.26, pConclusions We developed the model to analyze the invasion features of glioma cells. The significant suppression of glioma cell invasion by NSC23766 in brain slices indicates that anti-Rac1 treatment may represent an important future therapeutic strategy for glioblastoma.

Through the discussion of the mobile IPv6 intrusion detection model, analysis of mobile IPv6 communication technology, the solutions are given to prevent mobile IPv6 network intrusion behavior for providing the security policy.

The concise syntheses of three new natural diphyllin L-arabinopyranosides, Phyllanthusmin D (1), Phyllanthusmin B (4), Phyllanthusmin C (6) and a known analogue 7-O-[(2,3,4-tri-O-acetyl)-α-Larabinopyranosyl)] diphyllin (7) have been achieved employing phase transfer catalysis glycosylation and orthoester rearrangement. In biological assays, 4 showed the best cytotoxicity against human gastric carcinoma MGC803 Cells with the IC50 value 39 μg/mL. Transwell invasion assay showed that glycosides 1, 4, and 7 significantly suppressed MGC-803 cell invasion compared with control.

BACKGROUND The natural compound Curcumin was known to inhibit migration and invasion of glioblastoma (GBM) cells. Fascin, a kind of actin-binding proteins, is correlated with migration and invasion of GBM cells. The purpose of this study was to investigate anti-migration and anti-invasion effects of Curcumin via suppression of fascin expression in GBM cells. MATERIAL AND METHODS U87 cell line was used as an experimental model of GBM. Fascin was quantified by Western blot analysis. And, the signal transducer and activator of transcription 3 (STAT3), known to play an important role in migration and invasion of tumor cells, were analyzed by sandwich-ELISA. Migration and invasion capacities were assessed by attachment, migration and invasion assays. Cellular morphology was demonstrated by immunofluorescence. RESULTS At various concentrations of curcumin and exposure times, fascin expression decreased. After temporarily exposure to 10μM/L Curcumin during 6 hours as less invasive concentration and time, fascin expression temporarily decreased at 12 hours (18.4%, p=0.024), and since then recovered. And, the change of phosphrylated STAT3 level also reflected the temporarily decreased pattern of fascin expression at 12 hours (19.7%, p=0.010). Attachment, migration, and invasion capacities consistently decreased at 6, 12, and 24 hours. And, immunofluorescence showed the change of shape and the reduction of filopodia formation in cells. CONCLUSION Curcumin is likely to suppress the fascin expression in GBM cells, and this might be a possible mechanism for anti-migration and anti-invasion effects of Curcumin via inhibition of STAT3 phosphorylation.

APN inhibitors have been considered as potential anticancer agents for years. LB-4b is the first synthetic APN inhibitor to be evaluated for both of its anti-invasion and anti-angiogenesis effects. As a potent synthetic APN inhibitor (IC50=850 nM, versus bestatin of 8.1 μM), LB-4b was determined to have more significant block effects to cancer cell invasion and angiogenesis than bestatin. Besides, it is able to be easily synthesized with a high total yield, while the reported synthetic methods of bestatin are much more complex.

Cancer is a disease characterized by abnormal growth of cells. One of the most common types of liver cancers is called hepatocellular carcinoma (HCC) which is highly metastatic. As most of cannabinoids have shown anticancer effect against different cell lines in a number of reports, a biological investigation of two cannabinoids, CB65 (CB2 receptor agonist) and ACEA (CB1 receptor agonist) was carried out in this study.In an attempt to find natural products as a new solution of cancer, this study was designed to investigate the potential antitumoral and anti-invasive activity of cannabinoids on HepG2 cells and the possible roles of matrix metalloproteinase-2 (MMP-2) and MMP-9 in its action.The researchers examined the effect of various concentrations of CB65 (CB2 receptor agonist) and ACEA (CB1 receptor agonist), on the cell proliferation, viability, and invasion as well as expression of MMP-2 and MMP-9 in HepG2 cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay, matrigel invasion assay, and western blotting method.The results revealed that both cannabinoids reduce cell viability, cell invasion as well as MMP-2 and MMP-9 expression in higher dose of 20 nM. Furthermore, higher concentrations of examined cannabinoids were more effective.These data suggest ACEA and CB65 as an option for novel treatment of hepatocellular cancer.Our findings may contribute to design of new therapeutic strategies for the management of HCC.

A series of butylphthalide derivatives (BPDs) 1–8 were isolated from the extract of the dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae). The cytotoxic activities of BPDs 1–8 were evaluated using a panel of human cancer cell lines. In addition, the SAR analysis and potential anti-invasion activities were investigated. The sp2 carbons at C-7 and C-7a appeared to be essential for the cytotoxic activities of BPDs. BPDs 5 and 6 remarkably inhibited the migration and invasion of cancer cells. The anti-invasion activity of dimer 6 was demonstrated to be significantly higher than monomer 5.

International audience; The synthesis and biological activity of chloroethyl pyrimidine nucleosides is presented. One of these new nucleosides analogues significantly inhibited cell proliferation, migration and invasion as tested in vitro on the A431 vulvar epidermal carcinoma cell line.

Strongylophorine-26 (1), a new meroditerpenoid that shows activity in an anti-invasion assay, has been isolated from the marine sponge Petrosia (Strongylophora) corticata collected in Papua New Guinea. The structure of 1 was elucidated by analysis of spectroscopic data.

Invasion and subsequent establishment of distant metastasis is the most life threatening consequence for patients with cancer. Last decade has seen a major expansion in our knowledge and the understanding of the molecular and cellular mechanisms in tumour invasion and metastasis. Such understanding may also lead to the exploration of anti invasion/metastasis strategies. Some agents have already shown early promise in combating these processes. This article summarises progress in the anti-invasion and metastasis research and treatment.

The resistance of cartilage to tumor invasion was studied with the use of a novel in vitro culture system. Articular cartilage obtained from fresh metacarpophalangeal joints of preadolescent bovines was used as a growth surface for human TE-85 osteosarcoma cells and foreskin fibroblasts. Cartilage disks formed the bottoms of stainless-steel cylinders, providing closed growth chambers for these cells. Both invasive osteosarcoma cells and normal fibroblasts were unable to penetrate viable, unextracted cartilage during a 2-week culture period. When cartilage was devitalized by freezing and thawing, the tissue remained resistant to invasion. Cartilage, extracted with either 1 or 3 M guanidine hydrochloride, was invaded by osteosarcoma cells, but not by control fibroblasts. Invasion by osteosarcoma cells into salt-extracted cartilage was abolished when low concentrations of a cartilage-derived, anti-invasion factor were added to the culture medium. These data provided evidence that the resistance of cartilage to tumor invasion is regulated in part by tissue-derived proteinase inhibitors.

In solid cancers, invasion and metastasis account for more than 90% of mortality. However, in the current armory of anticancer therapies, a specific category of anti-invasion and antimetastatic drugs is missing. Here, we coin the term ‘migrastatics’ for drugs interfering with all modes of cancer cell invasion and metastasis, to distinguish this class from conventional cytostatic drugs, which are mainly directed against cell proliferation. We define actin polymerization and contractility as target mechanisms for migrastatics, and review candidate migrastatic drugs. Critical assessment of these antimetastatic agents is warranted, because they may define new options for the treatment of solid cancers.