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Research Project
Centre of Marine Sciences
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Can macroalgae provide promising anti-tumoral compounds? A closer look at Cystoseira tamariscifolia as a source for antioxidant and anti-hepatocarcinoma compounds
Publication . Vizetto-Duarte, C; Custódio, Luísa; Acosta, Gerardo; Lago, João H. G.; Morais, Thiago R.; Sousa, Carolina Bruno de; Gangadhar, Katkam N.; Rodrigues, Maria Joao; Pereira, Hugo; Lima, Raquel T.; Vasconcelos, M. Helena; Barreira, Luísa; Rauter, Amélia P.; Albericioi, Fernando; Varela, J.
Marine organisms are a prolific source of drug leads in a variety of therapeutic areas. In the last few years, biomedical, pharmaceutical and nutraceutical industries have shown growing interest in novel compounds from marine organisms, including macroalgae. Cystoseira is a genus of Phaeophyceae (Fucales) macroalgae known to contain bioactive compounds. Organic extracts (hexane, diethyl ether, ethyl acetate and methanol extracts) from three Cystoseira species (C. humilis, C. tamariscifolia and C. usneoides) were evaluated for their total phenolic content, radical scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'- azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radicals, and antiproliferative activity against a human hepatocarcinoma cell line (HepG2 cells). C. tamariscifolia had the highest TPC and RSA. The hexane extract of C. tamariscifolia (CTH) had the highest cytotoxic activity (IC50 = 2.31 mu g/mL), and was further tested in four human tumor (cervical adenocarcinoma HeLa; gastric adenocarcinoma AGS; colorectal adenocarcinoma HCT-15; neuroblastoma SH-SY5Y), and two non-tumor (murine bone marrow stroma S17 and human umbilical vein endothelial HUVEC) cell lines in order to determine its selectivity. CTH strongly reduced viability of all tumor cell lines, especially of HepG2 cells. Cytotoxicity was particularly selective for the latter cells with a selectivity index = 12.6 as compared to non-tumor cells. Incubation with CTH led to a 2-fold decrease of HepG2 cell proliferation as shown by the bromodeoxyuridine (BrdU) incorporation assay. CTH-treated HepG2 cells presented also pro-apoptotic features, such as increased Annexin Wpropidium iodide (PI) binding and dose-dependent morphological alterations in DAPI-stained cells. Moreover, it had a noticeable disaggregating effect on 3D multicellular tumor spheroids. Deme boxy cystoketal chromane, a derivative of the meroditerpenoid cystoketal, was identified as the active compound in CTH and was shown to display selective in vitro cYtotoxicitY towards HepG2 cells.
LPS modulates the expression of iron-related immune genes in two Antarctic notothenoids
Publication . Martínez, Danixa Pamela; Sousa, Carmen; Oyarzún, Ricardo; Pontigo, Juan Pablo; Canario, Adelino; Power, Deborah; Vargas-Chacoff, Luis; Guerreiro, Pedro
The non-specific immunity can induce iron deprivation as a defense mechanism against potential bacterial pathogens, but little information is available as to its role in Antarctic fish. In this study the response of iron metabolism related genes was evaluated in liver and head kidney of the Antarctic notothenoids Notothenia coriiceps and Notothenia rossii 7 days after lipopolysaccharide (LPS) injection. Average plasma Fe2+ concentration was unaffected by treatment in any of the species. The gene expression response to LPS varied between tissues and species, being stronger in N. coriiceps and more prominent in the head kidney than liver. The reaction to LPS was marked by increased individual variability in most genes analyzed, even when the change in expression was not statistically significant, suggesting different individual sensitivity and coping responses in these wild fish. We found that iron related genes had an attenuated and homogenous response to LPS but there was no detectable relationship between plasma Fe2+ and gene expression. However, overall in both tissues and species LPS exposure set a multilevel response that concur to promote intracellular accumulation of iron, an indication that Antarctic Notothenoids use innate nutritional immunity as a resistance mechanism against pathogens.
First report of the nutritional profile and antioxidant potential of Holothuria arguinensis, a new resource for aquaculture in Europe
Publication . Roggatz, Christina C.; Gonzalez-Wangueemert, Mercedes; Pereira, Hugo; Rodrigues, Maria Joao; F. G. M. Silva, Manuela; Barreira, Luísa; Varela, João; Custódio, Luísa
This work reports for the first time the nutritional profile and antioxidant potential of the edible sea cucumber Holothuria arguinensis from the North-eastern Atlantic. H. arguinensis has high levels of protein, with the amino acids profile dominated by alanine, glycine and proline and low lysine/arginine ratios. Its carbohydrate and energetic contents are also low as well as the total lipid levels, although its lipid profile is rich in polyunsaturated fatty acids (PUFA), especially arachidonic, eicosapentaenoic and docosahexaenoic acids. In addition, H. arguinensis has high levels of calcium. The water and ethanol extracts show ability to scavenge free radicals and to chelate copper and iron ions. Our results indicate that H. arguinensis has a balanced nutritional quality suitable for human consumption. In addition, it contains compounds with antioxidant potential; thus its intake can contribute for a healthy and well-balanced diet.[GRAPHICS].
Oestrogen, an evolutionary conserved regulator of T cell differentiation and immune tolerance in jawed vertebrates?
Publication . Paiola, Matthieu; Knigge, Thomas; Duflot, Aurélie; Pinto, Patricia IS; Farcy, Emilie; Monsinjon, Tiphaine
In teleosts, as in mammals, the immune system is tightly regulated by sexual steroid hormones, such as oestrogens. We investigated the effects of 17β-oestradiol on the expression of several genes related to T cell development and resulting T cell subpopulations in sea bass, Dicentrarchus labrax, for a primary lymphoid organ, the thymus, and two secondary lymphoid organs, the head-kidney and the spleen. In parallel, the oxidative burst capacity was assessed in leucocytes of the secondary lymphoid organs. Apoptosis- and proliferation-related genes, indicative of B and T cell clonal selection and lymphoid progenitor activity, were not affected by elevated oestrogen-levels. Sex-related oestrogen-responsiveness in T cell and antigen-presenting cell markers was observed, the expression of which was differentially induced by oestrogen-exposure in the three lymphoid organs. Remarkably, in the spleen, oestrogen increased regulatory T cell-related gene expression was associated with a decrease in oxidative burst capacity. To the best of our knowledge, this study indicates for the first time that physiological levels of oestrogen are likely to promote immune tolerance by modulating thymic function (i.e., T cell development and output) and peripheral T cells in teleosts, similar to previously reported oestrogenic effects in mammals.
Effect of light quality supplied by light emitting diodes (LEDs) on growth and biochemical profiles of Nannochloropsis oculata and Tetraselmis chuii
Publication . Schulze, Peter S.C.; Pereira, Hugo; Schueler, Lisa; Guerra, Rui Manuel Farinha das Neves; Barreira, Luísa; Perales, Jose A.; Varela, João; Santos, Tamara
Biochemical components obtained by microalgal biomass can be induced by specific wavelengths and processed to high value food/feed supplements or pharma- and nutraceuticals. Two biotechnologically relevant microalgae, Nannochloropsis oculata and Tetraselmis chuii, were exposed to non-tailored LEDs light sources emitting either mono- or multichromatic light with low red but significant blue (<450 nm) photon content, or tailored light sources with high blue or high red photon emissions: fluorescent light (FL), di- or multichromatic LED mixes. Growth of N. oculata and T. chuii under tailored light resulted in a approximate to 24% increase of the average biomass productivity as compared to cultures lit by non-tailored light sources. FL induced the highest C:N ratios in both algae (N. oculata: 7.91 +/- 0.09 and T. chuii: 11.29 +/- 0.03), highest total lipid (48.37 +/- 1.07%) in N. oculata and carbohydrate (55.31 +/- 1.02%) in T. chuii biomass. Among non-tailored light sources, monochromatic LEDs with emission peaks 465, 630 and 660 nm induced a approximate to 29% increase of carbohydrates and a approximate to 20% decrease of protein levels as compared to LEDs peaking at 405 nm and cool-and warm white LEDs. In conclusion, as FL have low photon conversion efficiencies (PCE), particularly within the red wavelength range, LEDs emitting at the 390-450 and 630-690 nm wavebands should be combined for optimal carbon fixation, nitrogen and phosphate uptake. (C) 2016 Elsevier B.V. All rights reserved.
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Funding agency
Fundação para a Ciência e a Tecnologia
Funding programme
6817 - DCRRNI ID
Funding Award Number
UID/Multi/04326/2013