{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T04:53:02Z","timestamp":1777697582070,"version":"3.51.4"},"reference-count":34,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2018,2,15]],"date-time":"2018-02-15T00:00:00Z","timestamp":1518652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Despite the increasing availability of new classes of cancer treatment, such as immune- and targeted therapies, there remains a need for the development of new antiproliferative\/cytotoxic drugs with improved pharmacological profiles that can also overcome drug resistant forms of cancer. In this study, we have identified, and characterised, a novel marine polysaccharide with the potential to be developed as an anticancer agent. Sulphated polysaccharides isolated from the common cockle (Cerastoderma edule) were shown to have antiproliferative activity on chronic myelogenous leukaemia and relapsed acute lymphoblastic leukaemia cell lines. Disaccharide and monosaccharide analysis of these marine polysaccharides confirmed the presence of glycosaminoglycan-like structures that were enriched in ion-exchange purified fractions containing antiproliferative activity. The antiproliferative activity of these glycosaminoglycan-like marine polysaccharides was shown to be susceptible to heparinase but not chondrotinase ABC digestion. This pattern of enzymatic and antiproliferative activity has not previously been seen, with either marine or mammalian glycosaminoglycans. As such, our findings suggest we have identified a new type of marine derived heparan sulphate\/heparin-like polysaccharide with potent anticancer properties.<\/jats:p>","DOI":"10.3390\/md16020063","type":"journal-article","created":{"date-parts":[[2018,2,20]],"date-time":"2018-02-20T03:54:22Z","timestamp":1519098862000},"page":"63","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Antiproliferative Activity of Glycosaminoglycan-Like Polysaccharides Derived from Marine Molluscs"],"prefix":"10.3390","volume":"16","author":[{"given":"Abdullah Faisal","family":"Aldairi","sequence":"first","affiliation":[{"name":"School of Environment and Life Sciences, Cockcroft Building, University of Salford, Manchester M5 4WT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olanrewaju Dorcas","family":"Ogundipe","sequence":"additional","affiliation":[{"name":"School of Environment and Life Sciences, Cockcroft Building, University of Salford, Manchester M5 4WT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David Alexander","family":"Pye","sequence":"additional","affiliation":[{"name":"School of Environment and Life Sciences, Cockcroft Building, University of Salford, Manchester M5 4WT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1002\/(SICI)1521-1878(199802)20:2<156::AID-BIES8>3.0.CO;2-R","article-title":"Glycosaminoglycan-protein interactions: Definition of consensus sites in glycosaminoglycan binding proteins","volume":"20","author":"Hileman","year":"1998","journal-title":"Bioessays"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.2174\/092986706777452470","article-title":"Therapeutic applications of glycosaminoglycans","volume":"13","author":"Volpi","year":"2006","journal-title":"Curr. Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S1877-1173(10)93001-9","article-title":"Glycosaminoglycan (gag) biosynthesis and gag-binding proteins","volume":"93","author":"Zhang","year":"2010","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1111\/joim.12061","article-title":"Pathophysiology of heparan sulphate: Many diseases, few drugs","volume":"273","author":"Lindahl","year":"2013","journal-title":"J. Intern. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/978-1-4899-2444-5_5","article-title":"Heparan sulphate proteoglycans: Molecular organisation of membrane\u2014Associated species and an approach to polysaccharide sequence analysis","volume":"313","author":"Gallagher","year":"1992","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"0589","DOI":"10.1098\/rsif.2015.0589","article-title":"Heparan sulfate and heparin interactions with proteins","volume":"12","author":"Meneghetti","year":"2015","journal-title":"J. R. Soc. Interface"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.biotechadv.2017.07.008","article-title":"Glycosaminoglycans from marine sources as therapeutic agents","volume":"35","author":"Valcarcel","year":"2017","journal-title":"Biotechnol. Adv."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2435","DOI":"10.3390\/md8092435","article-title":"Marine polysaccharides in pharmaceutical applications: An overview","volume":"8","author":"Laurienzo","year":"2010","journal-title":"Mar. Drugs"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8131","DOI":"10.1039\/C3RA23373A","article-title":"Fucoidans from brown seaweeds: An update on structures, extraction techniques and use of enzymes as tools for structural elucidation","volume":"3","author":"Ale","year":"2013","journal-title":"RSC Adv."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1007\/s10517-007-0226-4","article-title":"Antitumor and antimetastatic activity of fucoidan, a sulfated polysaccharide isolated from the okhotsk sea fucus evanescens brown alga","volume":"143","author":"Alekseyenko","year":"2007","journal-title":"Bull. Exp. Biol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.ijbiomac.2011.05.009","article-title":"Fucoidan from Sargassum sp. and Fucus vesiculosus reduces cell viability of lung carcinoma and melanoma cells in vitro and activates natural killer cells in mice in vivo","volume":"49","author":"Ale","year":"2011","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"225","DOI":"10.4062\/biomolther.2014.136","article-title":"Antitumor effects of fucoidan on human colon cancer cells via activation of akt signaling","volume":"23","author":"Han","year":"2015","journal-title":"Biomol. Ther."},{"key":"ref_13","first-page":"41","article-title":"[Antiviral activity of sulfated polysaccharide from the brown algae laminaria japonica against avian influenza a (h5n1) virus infection in the cultured cells]","volume":"55","author":"Makarenkova","year":"2010","journal-title":"Vopr. Virusol."},{"key":"ref_14","first-page":"443","article-title":"Fucoidan inhibits leukocyte recruitment in a model peritoneal inflammation in rat and blocks interaction of p-selectin with its carbohydrate ligand","volume":"43","author":"Preobrazhenskaya","year":"1997","journal-title":"Biochem. Mol. Biol. Int."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.thromres.2010.02.011","article-title":"Higher specificity of the activity of low molecular weight fucoidan for thrombin-induced platelet aggregation","volume":"125","author":"Zhu","year":"2010","journal-title":"Thromb. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.carbpol.2014.05.091","article-title":"Fucosylated chondroitin sulfate diversity in sea cucumbers: A review","volume":"112","author":"Myron","year":"2014","journal-title":"Carbohydr. Polym."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"50799","DOI":"10.1074\/jbc.M404746200","article-title":"Structural and functional characterization of oversulfated chondroitin sulfate\/dermatan sulfate hybrid chains from the notochord of hagfish. Neuritogenic and binding activities for growth factors and neurotrophic factors","volume":"279","author":"Nandini","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2967","DOI":"10.3390\/md13052967","article-title":"Marine polysaccharides from algae with potential biomedical applications","volume":"13","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11750","DOI":"10.1074\/jbc.271.20.11750","article-title":"A new glycosaminoglycan from the giant african snail Achatina fulica","volume":"271","author":"Kim","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4876","DOI":"10.3390\/md11124876","article-title":"Anticancer and cancer preventive properties of marine polysaccharides: Some results and prospects","volume":"11","author":"Fedorov","year":"2013","journal-title":"Mar. Drugs"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.3390\/molecules13081671","article-title":"Fucoidan: Structure and bioactivity","volume":"13","author":"Li","year":"2008","journal-title":"Molecules"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10719-009-9251-z","article-title":"Structural and functional insights into sulfated galactans: A systematic review","volume":"27","author":"Pomin","year":"2010","journal-title":"Glycoconj. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"29R","DOI":"10.1093\/glycob\/cwg058","article-title":"Sulfated fucans, fresh perspectives: Structures, functions, and biological properties of sulfated fucans and an overview of enzymes active toward this class of polysaccharide","volume":"13","author":"Berteau","year":"2003","journal-title":"Glycobiology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1016\/j.carres.2005.05.018","article-title":"Structure and anticoagulant activity of a sulfated galactan from the red alga, gelidium crinale. Is there a specific structural requirement for the anticoagulant action?","volume":"340","author":"Pereira","year":"2005","journal-title":"Carbohydr. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"232","DOI":"10.3390\/md12010232","article-title":"Holothurian fucosylated chondroitin sulfate","volume":"12","author":"Pomin","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kozlowski, E.O., Lima, P.C., Vicente, C.P., Lotufo, T., Bao, X., Sugahara, K., and Pav\u00e3o, M.S. (2011). Dermatan sulfate in tunicate phylogeny: Order-specific sulfation pattern and the effect of [\u21924idoa(2-sulfate)\u03b2-1\u21923galnac(4-sulfate)\u03b2-1\u2192] motifs in dermatan sulfate on heparin cofactor ii activity. BMC Biochem., 12.","DOI":"10.1186\/1471-2091-12-29"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"27848","DOI":"10.1074\/jbc.273.43.27848","article-title":"Highly sulfated dermatan sulfates from ascidians. Structure versus anticoagulant activity of these glycosaminoglycans","volume":"273","author":"Aiello","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.carbpol.2013.08.063","article-title":"A non-hemorrhagic hybrid heparin\/heparan sulfate with anticoagulant potential","volume":"99","author":"Brito","year":"2014","journal-title":"Carbohydr. Polym."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7312","DOI":"10.1074\/jbc.M109.091546","article-title":"Unique extracellular matrix heparan sulfate from the bivalve Nodipecten nodosus (linnaeus, 1758) safely inhibits arterial thrombosis after photochemically induced endothelial lesion","volume":"285","author":"Gomes","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1093\/glycob\/cwn028","article-title":"A simplified and sensitive fluorescent method for disaccharide analysis of both heparan sulfate and chondroitin\/dermatan sulfates from biological samples","volume":"18","author":"Deakin","year":"2008","journal-title":"Glycobiology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1093\/glycob\/cwi064","article-title":"Compositional profiling of heparin\/heparan sulfate using mass spectrometry: Assay for specificity of a novel extracellular human endosulfatase","volume":"15","author":"Saad","year":"2005","journal-title":"Glycobiology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"755","DOI":"10.3892\/ol_00000132","article-title":"Effect of fraxiparine, a type of low molecular weight heparin, on the invasion and metastasis of lung adenocarcinoma a549 cells","volume":"1","author":"Yu","year":"2010","journal-title":"Oncol. Lett."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/0003-2697(88)90089-9","article-title":"Monosaccharide analysis of glycoconjugates by anion exchange chromatography with pulsed amperometric detection","volume":"170","author":"Hardy","year":"1988","journal-title":"Anal. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"33674","DOI":"10.1074\/jbc.M804288200","article-title":"Evolutionary differences in glycosaminoglycan fine structure detected by quantitative glycan reductive isotope labeling","volume":"283","author":"Lawrence","year":"2008","journal-title":"J. Biol. Chem."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/16\/2\/63\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T14:55:19Z","timestamp":1760194519000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/16\/2\/63"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,15]]},"references-count":34,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2018,2]]}},"alternative-id":["md16020063"],"URL":"https:\/\/doi.org\/10.3390\/md16020063","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,15]]}}}