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      Antitumour Potential of Gigartina pistillata Carrageenans against Colorectal Cancer Stem Cell-Enriched Tumourspheres

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          Abstract

          Gigartina pistillata is a red seaweed common in Figueira da Foz, Portugal. Here, the antitumour potential of G. pistillata carrageenan, with a known variable of the life cycle, the female gametophyte (FG) and tetrasporophyte (T) was evaluated against colorectal cancer stem cell (CSC) -enriched tumourspheres. FTIR-ATR analysis of G. pistillata carrageenan extracts indicated differences between life cycle phases, being FG a κ/ι hybrid carrageenan and T a ʎ/ξ hybrid. Both carrageenan extracts presented IC 50 values inferior to 1 μg/mL in HT29-derived CSC-enriched tumourspheres, as well as reduced tumoursphere area. The two extracts were also effective at reducing cellular viability in SW620- and SW480-derived tumourspheres. These results indicate that carrageenans extracted from two G. pistillata life cycle phases have antitumour potential against colorectal cancer stem-like cells, specially the T carrageenan.

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          Most cited references 35

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          Antioxidant activities of sulfated polysaccharides from brown and red seaweeds

          The in vitro antioxidant activities of the following six sulfated polysaccharides were investigated: iota, kappa and lambda carrageenans, which are widely used in the food industry, fucoidan (homofucan) from the edible seaweed Fucus vesiculosus and fucans (heterofucans) F0.5 and F1.1 from the seaweed Padina gymnospora. With respect to the inhibition of superoxide radical formation, fucoidan had an IC50 (the half maximal inhibitory concentration) of 0.058 mg·mL−1, while the IC50 for the kappa, iota and lambda carrageenans were 0.112, 0.332 and 0.046 mg·mL−1, respectively. All of the samples had an inhibitory effect on the formation of hydroxyl radicals. The results of peroxidation tests showed that fucoidan had an IC50 of 1.250 mg·mL−1 and that the kappa, iota and lambda carrageenans had an IC50 of 2.753 and 2.338 and 0.323 mg·mL−1, respectively. Fucan fractions showed low antioxidant activity relative to fucoidan. These results clearly indicate the beneficial effect of algal polysaccharides as antioxidants.
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            Colon cancer: cancer stem cells markers, drug resistance and treatment.

            Malignant tumours consist of heterogeneous populations of tumour cells. Cancer stem cells (CSC) represent a population of cells within a tumour with highly tumorigenic and chemoresistant properties. These cells may be identified by the expression of CSC markers. There are several key stem cells markers specified for colon cancer: CD133, CD44, ALDH1, ALCAM. These days, a major obstacle to effective cancer management is development of a multidrug resistance (MDR). The principal mechanism responsible for development of MDR phenotype is the over-expression of ABC transporters. Tumours and relapsing tumours after therapy are drived by subpopulations of tumour cells with aggressive phenotype resistant to chemotherapeutics. These cells are called CSC or tumour-initiating cells (TIC). Here we outline recent information about MDR of colon cancer and CSC markers. We have focused on novel therapeutic strategies which have been developed to prevent or overcome MDR. One such strategy is a combination of chemotherapy and modulators of MDR pumps or chemotherapy and monoclonal antibodies against vascular endothelial growth factor VEGF. Colon cancer is characterized by the presence of colon CSC expressing specific stem cell markers. The divergent presence of these markers can help to adjust personalized therapy. The review provides a detailed overview of resistance of colon cancer cells and discusses how the presence of CSC markers can influence therapy and prognosis of patients.
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              Carrageenan: a review

              Carrageenan is a natural carbohydrate (polysaccharide) obtained from edible red seaweeds. The name Carrageenan is derived from the Chondrus crispus species of seaweed known as Carrageen Moss or Irish Moss in England, and Carraigin in Ireland. Carraigin has been used in Ireland since 400 AD as a gelatin and as a home remedy to cure coughs and colds. It grows along the coasts of North America and Europe. Carrageenans are used in a variety of commercial applications as gelling, thickening, and stabilising agents, especially in food products and sauces. Aside from these functions, carrageenans are used in experimental medicine, pharmaceutical formulations, cosmetics, and industrial applications.  
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                Author and article information

                Journal
                Mar Drugs
                Mar Drugs
                marinedrugs
                Marine Drugs
                MDPI
                1660-3397
                12 January 2020
                January 2020
                : 18
                : 1
                Affiliations
                [1 ]MARE—Marine and Environmental Sciences Centre, Faculty of Science and Technology, University of Coimbra, 3001-456 Coimbra, Portugal; jcotas@ 123456gmail.com
                [2 ]Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, University of Lisboa, 1649-003 Lisboa, Portugal; vismsmarques@ 123456ff.ulisboa.pt (V.M.); mbafonso@ 123456ff.ulisboa.pt (M.B.A.); cmprodrigues@ 123456ff.ulisboa.pt (C.M.P.R.)
                [3 ]Department of Life Sciences, University of Coimbra, 3000-456 Coimbra, Portugal
                Author notes
                [* ]Correspondence: leonel@ 123456bot.uc.pt ; Tel.: +351-239-855-229
                [†]

                These authors contributed equally to this work.

                Article
                marinedrugs-18-00050
                10.3390/md18010050
                7024308
                31940929
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

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