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1.
Carbohydr Polym ; 250: 116869, 2020 Dec 15.
Article in English | MEDLINE | ID: mdl-33049818

ABSTRACT

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.


Subject(s)
Galactans/pharmacology , Green Chemistry Technology , Melanoma, Experimental/prevention & control , Seaweed/chemistry , Sulfates/chemistry , Animals , Apoptosis , Cell Proliferation , Female , Humans , Male , Melanoma, Experimental/secondary , Mice , Mice, Inbred C57BL , Tumor Cells, Cultured
2.
Mar Biotechnol (NY) ; 22(2): 194-206, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31970542

ABSTRACT

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.


Subject(s)
Chlorophyta/chemistry , Deoxy Sugars/pharmacology , Mannans/pharmacology , Melanoma/drug therapy , Animals , Cell Line, Tumor , Cell Movement , Deoxy Sugars/toxicity , Mannans/toxicity , Mice , Neoplasm Invasiveness , Sulfates
3.
Braz J Med Biol Res ; 51(10): e7417, 2018 Aug 16.
Article in English | MEDLINE | ID: mdl-30156610

ABSTRACT

It is well known that the aminoglycoside antibiotic gentamicin is capable of causing damage to kidney cells. Given the known involvement of Ca2+ in the nephrotoxic action of gentamicin, the purpose of this study was to establish a relationship between the concentration of intracellular Ca2+ ([Ca2+]i) and cellular cytotoxicity using MDCK-C11 cells, a clone that has several properties that resemble those of intercalated cells of the distal nephron. Changes in [Ca2+]i was determined using fluorescence microscopy. Cell viability was evaluated by the neutral red method, and cell cytotoxicity by the MTT method. The [Ca2+]i gradually increased when cells were exposed to 0.1 mM gentamicin for 10, 20, and 30 min. The presence of extracellular Ca2+ was found to be necessary to stimulate the increase in [Ca2+]i induced by gentamicin, since this stimulus disappeared by using 1.8 mM EGTA (a Ca2+ chelator). Morphological changes were observed with scanning electron microscopy in epithelial cells exposed to the antibiotic. Furthermore, with the MTT method, a decrease in metabolic activity induced by gentamicin was observed, which indicates a cytotoxic effect. In conclusion, gentamicin was able to alter [Ca2+]i, change the morphology of MDCK-C11 cells, and promote cytotoxicity.


Subject(s)
Anti-Bacterial Agents/toxicity , Calcium/metabolism , Gentamicins/toxicity , Madin Darby Canine Kidney Cells/drug effects , Toxicity Tests/methods , Animals , Cell Membrane/metabolism , Cell Survival/drug effects , Clone Cells , Dogs , Madin Darby Canine Kidney Cells/metabolism , Madin Darby Canine Kidney Cells/ultrastructure , Microscopy, Electron, Scanning , Models, Animal , Nephrons/cytology , Nephrons/drug effects
4.
Braz. j. med. biol. res ; 51(10): e7417, 2018. graf
Article in English | LILACS | ID: biblio-951710

ABSTRACT

It is well known that the aminoglycoside antibiotic gentamicin is capable of causing damage to kidney cells. Given the known involvement of Ca2+ in the nephrotoxic action of gentamicin, the purpose of this study was to establish a relationship between the concentration of intracellular Ca2+ ([Ca2+]i) and cellular cytotoxicity using MDCK-C11 cells, a clone that has several properties that resemble those of intercalated cells of the distal nephron. Changes in [Ca2+]i was determined using fluorescence microscopy. Cell viability was evaluated by the neutral red method, and cell cytotoxicity by the MTT method. The [Ca2+]i gradually increased when cells were exposed to 0.1 mM gentamicin for 10, 20, and 30 min. The presence of extracellular Ca2+ was found to be necessary to stimulate the increase in [Ca2+]i induced by gentamicin, since this stimulus disappeared by using 1.8 mM EGTA (a Ca2+ chelator). Morphological changes were observed with scanning electron microscopy in epithelial cells exposed to the antibiotic. Furthermore, with the MTT method, a decrease in metabolic activity induced by gentamicin was observed, which indicates a cytotoxic effect. In conclusion, gentamicin was able to alter [Ca2+]i, change the morphology of MDCK-C11 cells, and promote cytotoxicity.


Subject(s)
Animals , Dogs , Gentamicins/toxicity , Calcium/metabolism , Toxicity Tests/methods , Madin Darby Canine Kidney Cells/drug effects , Anti-Bacterial Agents/toxicity , Microscopy, Electron, Scanning , Cell Membrane/metabolism , Cell Survival/drug effects , Clone Cells , Models, Animal , Madin Darby Canine Kidney Cells/metabolism , Madin Darby Canine Kidney Cells/ultrastructure , Nephrons/cytology , Nephrons/drug effects
5.
Carbohydr Polym ; 178: 95-104, 2017 Dec 15.
Article in English | MEDLINE | ID: mdl-29050620

ABSTRACT

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.


Subject(s)
Fungal Polysaccharides/pharmacology , Galactans/pharmacology , Melanoma/drug therapy , Pleurotus/chemistry , Animals , Fruiting Bodies, Fungal/chemistry , Magnetic Resonance Spectroscopy , Mice , Mice, Inbred C57BL
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