Green does not always mean go: A sulfated galactan from Codium isthmocladum green seaweed reduces melanoma metastasis through direct regulation of malignancy features.

Melanoma is the most lethal form of skin cancer, with a worldwide increase in incidence. Despite the increased overall survival of metastatic melanoma patients given recent advances in targeted and immunotherapy, it still has a poor prognosis and available treatment options carry diverse severe side effects. Polysaccharides from seaweed have been shown to exert antitumor activities. Here we show in vitro and in vivo antitumor activities of a sulfated homogalactan (named 3G4S) from Codium isthmocladum seaweed in the B16-F10 murine melanoma cell line. 3G4S did not induce cytotoxicity or proliferation changes; however, it was able to reduce solid tumor growth and metastasis, while not inducing side effects in mice. B16-F10 cells traits related to the metastatic cascade were also impaired by 3G4S, reducing cell invasion, colony-forming capacity and membrane glycoconjugates. Therefore, 3G4S shows promising antitumor activities without the commonly associated drawbacks of cancer treatments and can be further explored.

Non-Cytotoxic Sulfated Heterorhamnan from Gayralia brasiliensis Green Seaweed Reduces Driver Features of Melanoma Metastatic Progression.

Melanoma is a form of skin cancer with high mortality owing to its fast progression and metastatic capacity. The treatments available nowadays are only palliative in advanced stages of the disease. Thus, alternative therapies for cancer treatment are in demand, and molecules from natural sources, such as polysaccharides, could represent new possible therapeutic approaches. Polysaccharides of freshwater and marine algae with biological activities, such as antitumor properties, are greatly reported in the scientific literature. In the present study, a sulfated heterorhamnan obtained from the green seaweed Gayralia brasiliensis (Gb1 fraction) was chemically characterized and its biological activities in the B16-F10 murine melanoma cell line were evaluated. The Gb1 polysaccharidic fraction tested concentrations presented low or absence of cytotoxicity to B16-F10 cells and neither cell proliferation nor cell cycle were altered. Interestingly, Gb1 treatment decreased B16-F10 cells migration and invasion capabilities and CD44 labeling, showing to be a promising compound for further in vitro and in vivo antitumor studies.

Safe therapeutics of murine melanoma model using a novel antineoplasic, the partially methylated mannogalactan from Pleurotus eryngii.

A heteropolysaccharide was isolated by cold aqueous extraction from edible mushroom Pleurotus eryngii ("King Oyster") basidiocarps and its biological properties were evaluated. Structural assignments were carried out using mono- and bidimensional NMR spectroscopy, monosaccharide composition, and methylation analyses. A mannogalactan having a main chain of (1→6)-linked α-d-galactopyranosyl and 3-O-methyl-α-d-galactopyranosyl residues, both partially substituted at OH-2 by ß-d-Manp (MG-Pe) single-unit was found. Biological effects of mannogalactan from P. eryngii (MG-Pe) were tested against murine melanoma cells. MG-Pe was non-cytotoxic, but reduced in vitro melanoma cells invasion. Also, 50mg/kg MG-Pe administration to melanoma-bearing C57BL/6 mice up to 10days decreased in 60% the tumor volume compared to control. Additionally, no changes were observed when biochemical profile, complete blood cells count (CBC), organs, and body weight were analyzed. Mg-Pe was shown to be a promising anti-melanoma molecule capable of switching melanoma cells to a non-invasive phenotype with no toxicity to melanoma-bearing mice.

Microscopic diagnosis of the leaf and stem of Piper solmsianum C.DC.

Piper solmsianum C.DC., which is popularly known as pariparoba, is a shrub that measures 1-3 m in height and it inhabits areas with wet tropical soils. The objective of this study was to analyze the leaf and stem anatomy using light microscopy, scanning electron micrographs, and energy-dispersive X-ray spectroscopy in order to provide information for species identification. The anatomical profile showed the following main microscopic markers: hypostomatic leaf; hypodermis layer on both sides; pearl glands; biconvex midrib shape; five collateral vascular bundles in open arc with the central bundle larger than the others; circular stem shape; collateral vascular bundles arranged in two rings; sinuous sclerenchymatic sheath in the pith; secretory idioblasts; and starch grains in the mesophyll, in the ground parenchyma of the midrib, petiole, and in the stem; and six morphotypes of calcium oxalate crystals (styloids, cuneiform, tabular crystal rosettes, cuneiform crystal rosettes, elongated square dipyramids, as well as very elongated square dipyramids).

Female Sex Hormones Influence the Febrile Response Induced by Lipopolysaccharide, Cytokines and Prostaglandins but not by Interleukin-1ß in Rats.

There are differences in the immune response, and particularly fever, between males and females. In the present study, we investigated how the febrile responses induced by lipopolysaccharide (LPS) and different endogenous pyrogens were affected by female gonadal hormones. The febrile response to i.p. injection of LPS (50 µg/kg) was 40% lower in female rats compared to male or ovariectomised (OVX) female rats. Accordingly, oestrogen replacement in OVX animals reduced LPS-induced fever. Treatment with the prostaglandin synthesis inhibitor indomethacin (2 mg/kg, i.p. 30 min before) reduced the febrile response induced by LPS in both OVX (88%) and sham-operated (71%) rats. In line with the enhanced fever in OVX rats, there was increased expression of cyclooxygenase-2 (COX-2) in the hypothalamus and elevated levels of prostaglandin E2 (PGE2 ). In addition, OVX rats were hyper-responsive to PGE2 injected i.c.v. By contrast to the enhanced fever in response to LPS and PGE2 , the febrile response induced by i.c.v. injection of interleukin (IL)-1ß was unaffected by ovariectomy, whereas the responses induced by tumour necrosis factor (TNF)-α and macrophage inflammatory protein (MIP)-1α were completely abrogated. These results suggest that the mediators involved in the febrile response in females are similar to males, although the reduction of female hormones may decrease the responsiveness of some mediators such as TNF-α and MIP-1α. Compensatory mechanisms may be activated in females after ovariectomy such as an augmented synthesis of COX-2 and PGE2 .

Análise farmacobotânica de folha e caule de Tanacetum vulgare (L. ) / Pharmacobotanical analysis of leaf and stem of Tanacetum vulgare (L. )

RESUMO Tanacetum vulgare L., conhecida popularmente como catinga-de-mulata, é utilizada na medicina tradicional como vermífugo, digestivo e emenagogo. Objetivou-se analisar a morfoanatomia de folhas e caules dessa espécie medicinal com vistas ao controle da qualidade. Foram utilizadas técnicas usuais de microscopia de luz e eletrônica de varredura. As folhas são compostas, pinatissectas e anfiestomáticas. Tricomas tectores flageliformes simples e glandulares capitados são observados. A nervura central tem formato biconvexo, o pecíolo é côncavo-convexo, a ráque é plano-convexa e o caule é arredondado. Feixes vasculares colaterais, calotas de fibras perivasculares e colênquima lamelar estão presentes na folha e no caule. Os caracteres morfoanatômicos evidenciados contribuem na identificação do táxon e fornecem subsídios farmacobotânicos para o controle da qualidade de drogas vegetais e fitoterápicos.

ABSTRACT Tanacetum vulgare L., popularly known as tansy, is used in traditional medicine as a vermifuge, digestive and emmenagogue. This study aimed to analyze the morphoanatomical leaves and stems of this medicinal plant in order to control the quality. Usual techniques of light and scanning electron microscopy were used. The leaves are composed, pinatissect and amphistomatic. Simple and flagelliform non- glandular trichomes and capitate glandular trichomes are observed. The midrib has biconvex shape, the petiole is concavo-convex, the rachis is plano-convex, and the stem is rounded. Collateral vascular bundles, perivascular fiber caps and laminar collenchyma are encountered in the leaves and stems. Evidenced the morphological and anatomical features contribute to the identification of the taxon and provide pharmacobotanical data for the quality control of herbal drugs.

Baccharis rufescens Spreng. var. tenuifolia (DC. ) Baker: contribuição ao estudo farmacognóstico / Baccharis rufescens Spreng. var. tenuifolia (DC. ) Baker: contribution to the pharmacognostic study

Baccharis rufescens Spreng. var. tenuifolia (DC.) Baker pertence à família Asteraceae e é usada na medicina tradicional como estomáquico e hepatoprotetor. Um estudo fitoquímico mostrou a presença de flavonoides e triterpenos, sendo que os extratos clorofórmico e metanólico de folhas apresentaram-se ativos no bioensaio de toxicidade sobre Artemia salina Leach. Além disso, extratos clorofórmicos evidenciaram a presença de peróxidos, sugerindo sua aplicação no tratamento da malária (Schenkel at al., 2002; Montanher et al., 2002; Moreira et al., 2003). Considerando a importância farmacológica de B. rufescens var. tenuifolia, o presente trabalho objetivou o estudo morfoanatômico e histoquímico do caule e da folha dessa espécie, a fim de fornecer subsídios farmacognósticos para o controle de qualidade. O material botânico foi submetido às técnicas usuais empregadas na microscopia de luz e microscopia eletrônica de varredura. Folha anfiestomática, presença de estômatos anomocíticos, tricomas glandulares capitados bisseriados, tricomas tectores flageliformes simples unisseriados, dutos secretores associados ao floema, calota de fibras perivasculares e cristais de oxalato de cálcio do tipo estiloide e prismático na região medular do caule foram as principais características observadas que auxiliam na identificação do táxon.

Baccharis rufescens Spreng. var. tenuifolia (DC.) Baker belongs to the Asteraceae family. It is used for liver and stomach problems in traditional medicine. Previous phytochemical data reported flavonoid and triterpene contents. Chloroform and methanol extracts of the leaves showed activity in the bioassay of brine shrimp. Chloroform extracts showed the presence of peroxides that can be used to treat malaria (Schenkel et al., 2002; Montanher et al., 2002; Moreira et al., 2003). Considering the pharmacological importance of B. rufescens var. tenuifolia, the purpose of this paper was to perform the anatomical analysis of aerial vegetative parts of Baccharis rufescens var. tenuifolia in order to provide pharmacognostic data for quality control. The plant material was studied by the usual methods of light and scanning electron microscopy. Amphistomatic leaves, anomocytic stomata, biseriate capitate glandular trichomes, uniseriate simple flagelliform non-glandular trichomes, secretory ducts associated to the phloem, perivascular fiber cap, calcium oxalate as prismatic and styloid crystals in the pith of the stem were reported as the mainly anatomical data for B. rufescens var. tenuifolia.Ouvir Ler foneticamente.

Cell death and DNA damage in peritoneal macrophages of mice (Mus musculus) exposed to inorganic lead.

Lead is a heavy metal of considerable environmental and occupational concern and there is growing evidence that it is toxic to the human immune system. In this regard, this study examined the effect of lead (Pb) exposure to peritoneal macrophages (Mvarphis) of mice (Mus musculus) cultivated in DMEM medium supplemented with fetal bovine serum, in order to investigate cell damage related to cell death. Cells were exposed to two concentrations of inorganic lead [Pb(II)] for 4, 24 and 72h. Cell viability declined during the treatment, with responses including cell death, cellular damage and DNA damage. Cell death images were found in treated cells with an increase in Bax expression, but the inorganic lead failed to induce the loss of membrane asymmetry (Annexin V conjugates), suggesting that cell death was mainly due to necrosis induction. The effects of Pb(II) on the mechanisms of cell death is not completely understood, but the immunosuppression due to DNA damage and Mvarphis death is discussed here. We have previously shown the effect of inorganic lead in mitochondria and phagocytosis in Mvarphis, suggesting here a pathway for the effect of the metal on mechanisms of cell death, also discussing its effects on the immune system.

Cytotoxic effect of a new 1,3,4-thiadiazolium mesoionic compound (MI-D) on cell lines of human melanoma.

The structural characteristics of mesoionic compounds, which contain distinct regions of positive and negative charges associated with a poly-heteroatomic system, enable them to cross cellular membranes and interact strongly with biomolecules. Potential biological applications have been described for mesoionic compounds. 1,3,4-Thiadiazolium mesoionic compound (MI-D), a new mesoionic compound, has been demonstrated to be extremely cytotoxic to B16-F10 murine melanoma cells when compared to fotemustine and dacarbazine, drugs of reference in melanoma treatment protocols, describing inhibition of tumours grown in vitro and in vivo. We now evaluate the effects of mesoionic compound MI-D on different human melanoma cell lines. The drug decreased the viability and proliferation of MEL-85, SK-MEL, A2058 and MEWO cell lines in vitro, showing a considerable cytotoxic activity on these human cells. Adhesion of MEL-85 cells was evaluated in the presence of the drug using different extracellular matrix (ECM) constituents. MI-D decreased MEL-85 adhesion to laminin, fibronectin and matrigel. The morphology and actin cytoskeleton organisation of MEL-85 cells were also modified on MI-D treatment. These results on human melanoma cell lines indicate that MI-D is a very encouraging drug against melanoma, a tumour that is extremely resistant to chemotherapy.

Heparan sulfate and control of cell division: adhesion and proliferation of mutant CHO-745 cells lacking xylosyl transferase

We have examined the role of cell surface glycosaminoglycans in cell division: adhesion and proliferation of Chinese hamster ovary (CHO) cells. We used both wild-type (CHO-K1) cells and a mutant (CHO-745) which is deficient in the synthesis of proteoglycans due to lack of activity of xylosyl transferase. Using different amounts of wild-type and mutant cells, little adhesion was observed in the presence of laminin and type I collagen. However, when fibronectin or vitronectin was used as substrate, there was an enhancement in the adhesion of wild-type and mutant cells. Only CHO-K1 cells showed a time-dependent adhesion on type IV collagen. These results suggest that the two cell lines present different adhesive profiles. Several lines of experimental evidence suggest that heparan sulfate proteoglycans play a role in cell adhesion as positive modulators of cell proliferation and as key participants in the process of cell division. Proliferation and cell cycle assays clearly demonstrate that a decrease in the amount of glycosaminoglycans does not inhibit the proliferation of mutant CHO-745 cells when compared to the wild type CHO-K1, in agreement with the findings that both CHO-K1 and CHO-745 cells take 8 h to enter the S phase

A fucan from the brown seaweed Spatoglossum schröederi inhibits Chinese hamster ovary cell adhesion to several extracellular matrix proteins

Fucans, a family of sulfated polysaccharides present in brown seaweed, have several biological activities. Their use as drugs would offer the advantage of no potential risk of contamination with viruses or particles such as prions. A fucan prepared from Spatoglossum schröederi was tested as a possible inhibitor of cell-matrix interactions using wild-type Chinese hamster ovary cells (CHO-K1) and the mutant type deficient in xylosyltransferase (CHO-745). The effect of this polymer on adhesion properties with specific extracellular matrix components was studied using several matrix proteins as substrates for cell attachment. Treatment with the polymer inhibited the adhesion of fibronectin to both CHO-K1 (2 x 10(5))()and CHO-745 (2 x 10(5) and 5 x 10(5)) cells. No effect was detected with laminin, using the two cell types. On the other hand, adhesion to vitronectin was inhibited in CHO-K1 cells and adhesion to type I collagen was inhibited in CHO-745 cells. In spite of this inhibition, the fucan did not affect either cell proliferation or cell cycle. These results demonstrate that this polymer is a new anti-adhesive compound with potential pharmacological applications