{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:43:16Z","timestamp":1790779396392,"version":"4.1.0"},"reference-count":88,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T00:00:00Z","timestamp":1684368000000},"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>Angiogenesis and metastasis represent two challenging targets to combat cancer development in the later stages of its progression. Numerous studies have indicated the important role of natural products in blocking tumor angiogenesis signaling pathways in several advanced tumors. In recent years, the marine polysaccharides fucoidans emerged as promising anticancer compounds showing potent antitumor activity in both in vitro and in vivo models of different types of cancers. The objective of this review is to focus on the antiangiogenic and antimetastatic activities of fucoidans with special emphasis on preclinical studies. Independently from their source, fucoidans inhibit several angiogenic regulators, primarily vascular endothelial growth factor (VEGF). A glance towards fucoidans\u2019 ongoing clinical trials and pharmacokinetic profile is provided to present the main challenges that still need to be addressed for their bench-to-bedside translation.<\/jats:p>","DOI":"10.3390\/md21050307","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:55:29Z","timestamp":1684457729000},"page":"307","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Ten Years of Research on Fucoidan and Cancer: Focus on Its Antiangiogenic and Antimetastatic Effects"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4743-1126","authenticated-orcid":false,"given":"Eleonora","family":"Turrini","sequence":"first","affiliation":[{"name":"Department for Life Quality Studies, University of Bologna\u2014C.so d\u2019Augusto, 237, 47921 Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Maffei","sequence":"additional","affiliation":[{"name":"Department for Life Quality Studies, University of Bologna\u2014C.so d\u2019Augusto, 237, 47921 Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2461-8214","authenticated-orcid":false,"given":"Carmela","family":"Fimognari","sequence":"additional","affiliation":[{"name":"Department for Life Quality Studies, University of Bologna\u2014C.so d\u2019Augusto, 237, 47921 Rimini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.2991\/jegh.k.191008.001","article-title":"Current Cancer Epidemiology","volume":"9","author":"Mattiuzzi","year":"2019","journal-title":"J. Epidemiol. Glob. Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1634\/theoncologist.2014-0465","article-title":"Targeting Angiogenesis in Cancer Therapy: Moving Beyond Vascular Endothelial Growth Factor","volume":"20","author":"Zhao","year":"2015","journal-title":"Oncologist"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/S0140-6736(15)01088-0","article-title":"Antiangiogenic Therapy in Oncology: Current Status and Future Directions","volume":"388","author":"Jayson","year":"2016","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Catanzaro, E., Greco, G., Potenza, L., Calcabrini, C., and Fimognari, C. (2018). Natural Products to Fight Cancer: A Focus on Juglans Regia. Toxins, 10.","DOI":"10.3390\/toxins10110469"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lenzi, M., Cocchi, V., Novakovi\u0107, A., Karaman, M., Saka\u010d, M., Mandi\u0107, A., Poji\u0107, M., Barbalace, M.C., Angeloni, C., and Hrelia, P. (2018). Meripilus Giganteus Ethanolic Extract Exhibits Pro-Apoptotic and Anti-Proliferative Effects in Leukemic Cell Lines. BMC Complement. Altern. Med., 18.","DOI":"10.1186\/s12906-018-2366-7"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"503","DOI":"10.2174\/1570161115666170713094319","article-title":"Potential Role of Natural Compounds as Anti-Angiogenic Agents in Cancer","volume":"15","author":"Shanmugam","year":"2017","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Turrini, E., Maffei, F., and Fimognari, C. (2022). Effect of the Marine Polyketide Plocabulin on Tumor Progression. Mar. Drugs, 21.","DOI":"10.3390\/md21010038"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3371","DOI":"10.1002\/ptr.7492","article-title":"Pull the Plug: Anti-Angiogenesis Potential of Natural Products in Gastrointestinal Cancer Therapy","volume":"36","author":"Ai","year":"2022","journal-title":"Phytother. Res. PTR"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.biopha.2017.01.161","article-title":"Green Tea and Its Anti-Angiogenesis Effects","volume":"89","author":"Rashidi","year":"2017","journal-title":"Biomed. Pharmacother. Biomed. Pharmacother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"772915","DOI":"10.3389\/fonc.2021.772915","article-title":"Natural Products: A Promising Therapeutics for Targeting Tumor Angiogenesis","volume":"11","author":"Li","year":"2021","journal-title":"Front. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.ijbiomac.2022.09.055","article-title":"Advances in Anti-Cancer Effects and Underlying Mechanisms of Marine Algae Polysaccharides","volume":"221","author":"Yao","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.carbpol.2016.08.005","article-title":"A Review about the Development of Fucoidan in Antitumor Activity: Progress and Challenges","volume":"154","author":"Wu","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jff.2012.08.007","article-title":"Fucoidans as a Natural Bioactive Ingredient for Functional Foods","volume":"5","author":"Vo","year":"2013","journal-title":"J. Funct. Foods"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yang, J.-Y., and Lim, S.Y. (2021). Fucoidans and Bowel Health. Mar. Drugs, 19.","DOI":"10.3390\/md19080436"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.3390\/md13042327","article-title":"Fucoidan and Cancer: A Multifunctional Molecule with Anti-Tumor Potential","volume":"13","author":"Atashrazm","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Wang, Y., Xing, M., Cao, Q., Ji, A., Liang, H., and Song, S. (2019). Biological Activities of Fucoidan and the Factors Mediating Its Therapeutic Effects: A Review of Recent Studies. Mar. Drugs, 17.","DOI":"10.3390\/md17030183"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e15202","DOI":"10.1016\/j.heliyon.2023.e15202","article-title":"Anti-Inflammatory Properties of Antiangiogenic Fucoidan in Retinal Pigment Epithelium Cells","volume":"9","author":"Seeba","year":"2023","journal-title":"Heliyon"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"250","DOI":"10.2174\/1566524022666220321125548","article-title":"Anti-Diabetic Effects of Macronutrients via Modulation of Angiogenesis: A Comprehensive Review on Carbohydrates and Proteins","volume":"23","author":"Khosravifar","year":"2023","journal-title":"Curr. Mol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ijbiomac.2022.10.255","article-title":"A Fucoidan-Gelatin Wound Dressing Accelerates Wound Healing by Enhancing Antibacterial and Anti-Inflammatory Activities","volume":"223","author":"Lu","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Bae, H., Lee, J.-Y., Yang, C., Song, G., and Lim, W. (2020). Fucoidan Derived from Fucus Vesiculosus Inhibits the Development of Human Ovarian Cancer via the Disturbance of Calcium Homeostasis, Endoplasmic Reticulum Stress, and Angiogenesis. Mar. Drugs, 18.","DOI":"10.3390\/md18010045"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.3892\/mmr.2017.6338","article-title":"Antitumor Activity of Fucoidan in Anaplastic Thyroid Cancer via Apoptosis and Anti-Angiogenesis","volume":"15","author":"Shen","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"115034","DOI":"10.1016\/j.carbpol.2019.115034","article-title":"Fucoidan from Fucus Vesiculosus Inhibits New Blood Vessel Formation and Breast Tumor Growth in Vivo","volume":"223","author":"Oliveira","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wang, F., Schmidt, H., Pavleska, D., Wermann, T., Seekamp, A., and Fuchs, S. (2017). Crude Fucoidan Extracts Impair Angiogenesis in Models Relevant for Bone Regeneration and Osteosarcoma via Reduction of VEGF and SDF-1. Mar. Drugs, 15.","DOI":"10.3390\/md15060186"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.3892\/or.2016.4987","article-title":"Fucoidan Inhibits Angiogenesis Induced by Multiple Myeloma Cells","volume":"36","author":"Liu","year":"2016","journal-title":"Oncol. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4449","DOI":"10.21873\/anticanres.10989","article-title":"Silencing Prion Protein in HT29 Human Colorectal Cancer Cells Enhances Anticancer Response to Fucoidan","volume":"36","author":"Yun","year":"2016","journal-title":"Anticancer Res."},{"key":"ref_27","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_28","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.3390\/md13041882","article-title":"Prophylactic Administration of Fucoidan Represses Cancer Metastasis by Inhibiting Vascular Endothelial Growth Factor (VEGF) and Matrix Metalloproteinases (MMPs) in Lewis Tumor-Bearing Mice","volume":"13","author":"Huang","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Xue, M., Ge, Y., Zhang, J., Wang, Q., Hou, L., Liu, Y., Sun, L., and Li, Q. (2012). Anticancer Properties and Mechanisms of Fucoidan on Mouse Breast Cancer in Vitro and in Vivo. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0043483"},{"key":"ref_30","first-page":"330","article-title":"Fucoidan Inhibits Epithelial-to-Mesenchymal Transition via Regulation of the HIF-1\u03b1 Pathway in Mammary Cancer Cells under Hypoxia","volume":"18","author":"Li","year":"2019","journal-title":"Oncol. Lett."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rui, X., Pan, H.-F., Shao, S.-L., and Xu, X.-M. (2017). Anti-Tumor and Anti-Angiogenic Effects of Fucoidan on Prostate Cancer: Possible JAK-STAT3 Pathway. BMC Complement. Altern. Med., 17.","DOI":"10.1186\/s12906-017-1885-y"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.ijbiomac.2020.01.256","article-title":"Fucoidan from Laminaria Japonica Exerts Antitumor Effects on Angiogenesis and Micrometastasis in Triple-Negative Breast Cancer Cells","volume":"149","author":"Hsu","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6099","DOI":"10.3390\/md13106099","article-title":"Fucoidan Elevates MicroRNA-29b to Regulate DNMT3B-MTSS1 Axis and Inhibit EMT in Human Hepatocellular Carcinoma Cells","volume":"13","author":"Yan","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4436","DOI":"10.3390\/md13074436","article-title":"Low Molecular Weight Fucoidan Inhibits Tumor Angiogenesis through Downregulation of HIF-1\/VEGF Signaling under Hypoxia","volume":"13","author":"Chen","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4777","DOI":"10.7150\/jca.26740","article-title":"Antimetastatic Effect of Fucoidan-Sargassum against Liver Cancer Cell Invadopodia Formation via Targeting Integrin AV\u03b23 and Mediating AV\u03b23\/Src\/E2F1 Signaling","volume":"10","author":"Pan","year":"2019","journal-title":"J. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.canlet.2016.08.020","article-title":"Sulfated Fucoidan FP08S2 Inhibits Lung Cancer Cell Growth in Vivo by Disrupting Angiogenesis via Targeting VEGFR2\/VEGF and Blocking VEGFR2\/Erk\/VEGF Signaling","volume":"382","author":"Chen","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.carbpol.2015.09.087","article-title":"Structural Characterization and Effect on Anti-Angiogenic Activity of a Fucoidan from Sargassum Fusiforme","volume":"136","author":"Cong","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.ijbiomac.2014.12.031","article-title":"Fucoidan from Turbinaria Conoides: A Multifaceted \u201cdeliverable\u201d to Combat Pancreatic Cancer Progression","volume":"74","author":"Delma","year":"2015","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3514","DOI":"10.3390\/md13063514","article-title":"Fucoidan Suppresses Hypoxia-Induced Lymphangiogenesis and Lymphatic Metastasis in Mouse Hepatocarcinoma","volume":"13","author":"Teng","year":"2015","journal-title":"Mar. Drugs"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"38025","DOI":"10.18632\/oncotarget.9443","article-title":"Fucoidan Inhibits Lymphangiogenesis by Downregulating the Expression of VEGFR3 and PROX1 in Human Lymphatic Endothelial Cells","volume":"7","author":"Yang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Chen, X., Sun, L., Wei, X., Lu, H., Tan, Y., Sun, Z., and Jiang, J. (2021). Antitumor Effect and Molecular Mechanism of Fucoidan in NSCLC. BMC Complement. Med. Ther., 21.","DOI":"10.1186\/s12906-020-03191-0"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Hou, C.-Y., Ma, C.-Y., Lin, Y.-J., Huang, C.-L., Wang, H.-D., and Yuh, C.-H. (2022). WNK1-OSR1 Signaling Regulates Angiogenesis-Mediated Metastasis towards Developing a Combinatorial Anti-Cancer Strategy. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232012100"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Shin, S.-W., Jung, W., Choi, C., Kim, S.-Y., Son, A., Kim, H., Lee, N., and Park, H.C. (2018). Fucoidan-Manganese Dioxide Nanoparticles Potentiate Radiation Therapy by Co-Targeting Tumor Hypoxia and Angiogenesis. Mar. Drugs, 16.","DOI":"10.3390\/md16120510"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/j.0959-9673.2004.00396.x","article-title":"Current Methods for Assaying Angiogenesis in Vitro and in Vivo","volume":"85","author":"Staton","year":"2004","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"245","DOI":"10.2174\/1568009611313030003","article-title":"Oxygen-Independent Regulation of HIF-1: Novel Involvement of PI3K\/AKT\/MTOR Pathway in Cancer","volume":"13","author":"Agani","year":"2013","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_46","unstructured":"Martin, T.A., Ye, L., Sanders, A.J., Lane, J., and Jiang, W.G. (2013). Cancer Invasion and Metastasis: Molecular and Cellular Perspective, Landes Bioscience."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s11684-018-0656-6","article-title":"Epithelial-to-Mesenchymal Transition in Cancer: Complexity and Opportunities","volume":"12","author":"Zhang","year":"2018","journal-title":"Front. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3557","DOI":"10.7150\/jca.26350","article-title":"The Role of MicroRNAs in Hepatocellular Carcinoma","volume":"9","author":"Xu","year":"2018","journal-title":"J. Cancer"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6411","DOI":"10.1182\/blood-2008-07-170589","article-title":"MicroRNA-29b Induces Global DNA Hypomethylation and Tumor Suppressor Gene Reexpression in Acute Myeloid Leukemia by Targeting Directly DNMT3A and 3B and Indirectly DNMT1","volume":"113","author":"Garzon","year":"2009","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1093\/carcin\/bgs396","article-title":"Fucoidan Induces Changes in the Epithelial to Mesenchymal Transition and Decreases Metastasis by Enhancing Ubiquitin-Dependent TGF\u03b2 Receptor Degradation in Breast Cancer","volume":"34","author":"Hsu","year":"2013","journal-title":"Carcinogenesis"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"902","DOI":"10.21037\/atm.2020.02.157","article-title":"Invadopodia: Clearing the Way for Cancer Cell Invasion","volume":"8","author":"Augoff","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.brainresbull.2022.02.005","article-title":"The Chick Embryo Chorioallantoic Membrane as an Experimental Model to Study in Vivo Angiogenesis in Glioblastoma Multiforme","volume":"182","author":"Ribatti","year":"2022","journal-title":"Brain Res. Bull."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Yousaf, S., Ahmad, M., Wu, S., Zia, M.A., Ahmed, I., Iqbal, H.M.N., Liu, Q., and Rehman, S.U. (2022). Cellular Prion Protein Role in Cancer Biology: Is It A Potential Therapeutic Target?. Biomedicines, 10.","DOI":"10.3390\/biomedicines10112833"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"427","DOI":"10.2174\/1568009033481741","article-title":"Emerging Role of Endoglin (CD105) as a Marker of Angiogenesis with Clinical Potential in Human Malignancies","volume":"3","author":"Fonsatti","year":"2003","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.coemr.2020.02.004","article-title":"Cytokines and Janus Kinase\/Signal Transducer and Activator of Transcription Signaling in Prostate Cancer: Overview and Therapeutic Opportunities","volume":"10","author":"Canesin","year":"2020","journal-title":"Curr. Opin. Endocr. Metab. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"692549","DOI":"10.1155\/2013\/692549","article-title":"Fucoidan Inhibits the Growth of Hepatocellular Carcinoma Independent of Angiogenesis","volume":"2013","author":"Zhu","year":"2013","journal-title":"Evid.-Based Complement. Altern. Med. ECAM"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1186\/s12967-020-02624-1","article-title":"Heparanase and the Hallmarks of Cancer","volume":"18","author":"Jayatilleke","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1108992","DOI":"10.3389\/fphar.2023.1108992","article-title":"Antiangiogenic Drugs in Combination with Seaweed Fucoidan: A Mechanistic in Vitro and in Vivo Study Exploring the VEGF Receptor and Its Downstream Signaling Molecules in Hepatic Cancer","volume":"14","author":"Abdollah","year":"2023","journal-title":"Front. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1007\/s11172-022-3680-2","article-title":"Anti-Angiogenic Properties of Sulfated Polysaccharides Fucoidans and Their Analogs","volume":"71","author":"Anisimova","year":"2022","journal-title":"Russ. Chem. Bull."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1093\/glycob\/cwu063","article-title":"Fucoidans: Pro- or Antiangiogenic Agents?","volume":"24","author":"Ustyuzhanina","year":"2014","journal-title":"Glycobiology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.ijbiomac.2016.06.007","article-title":"Doxorubicin-Loaded Fucoidan Capped Gold Nanoparticles for Drug Delivery and Photoacoustic Imaging","volume":"91","author":"Manivasagan","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Fernandes, A.S., Oliveira, C., Reis, R.L., Martins, A., and Silva, T.H. (2022). Marine-Inspired Drugs and Biomaterials in the Perspective of Pancreatic Cancer Therapies. Mar. Drugs, 20.","DOI":"10.3390\/md20110689"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1387\/ijdb.103238ct","article-title":"Zebrafish Embryo, a Tool to Study Tumor Angiogenesis","volume":"55","author":"Tobia","year":"2011","journal-title":"Int. J. Dev. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/978-3-319-30654-4_11","article-title":"Imaging Cancer Angiogenesis and Metastasis in a Zebrafish Embryo Model","volume":"916","author":"Tulotta","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Tsai, H.-L., Tai, C.-J., Huang, C.-W., Chang, F.-R., and Wang, J.-Y. (2017). Efficacy of Low-Molecular-Weight Fucoidan as a Supplemental Therapy in Metastatic Colorectal Cancer Patients: A Double-Blind Randomized Controlled Trial. Mar. Drugs, 15.","DOI":"10.3390\/md15040122"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1126\/science.1232227","article-title":"Neutralizing Tumor-Promoting Chronic Inflammation: A Magic Bullet?","volume":"339","author":"Coussens","year":"2013","journal-title":"Science"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/nrclinonc.2015.105","article-title":"Inflammation and Cancer: Advances and New Agents","volume":"12","author":"Crusz","year":"2015","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1177\/1534735417692097","article-title":"An Exploratory Study on the Anti-Inflammatory Effects of Fucoidan in Relation to Quality of Life in Advanced Cancer Patients","volume":"17","author":"Takahashi","year":"2018","journal-title":"Integr. Cancer Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"115323","DOI":"10.1016\/j.bcp.2022.115323","article-title":"Cisplatin in Cancer Treatment","volume":"206","author":"Romani","year":"2022","journal-title":"Biochem. Pharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.4236\/jct.2015.611111","article-title":"Effect of Fucoidan Dietary Supplement on the Chemotherapy Treatment of Patients with Unresectable Advanced Gastric Cancer","volume":"6","author":"Ikeguchi","year":"2015","journal-title":"J. Cancer Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1177\/1534735416684014","article-title":"The Effect of Undaria Pinnatifida Fucoidan on the Pharmacokinetics of Letrozole and Tamoxifen in Patients With Breast Cancer","volume":"17","author":"Tocaciu","year":"2018","journal-title":"Integr. Cancer Ther."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Shikov, A.N., Flisyuk, E.V., Obluchinskaya, E.D., and Pozharitskaya, O.N. (2020). Pharmacokinetics of Marine-Derived Drugs. Mar. Drugs, 18.","DOI":"10.3390\/md18110557"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s00343-015-4273-9","article-title":"Microanalysis and Preliminary Pharmacokinetic Studies of a Sulfated Polysaccharide from Laminaria Japonica","volume":"34","author":"Zhang","year":"2016","journal-title":"Chin. J. Oceanol. Limnol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.thromres.2016.03.008","article-title":"Antithrombotic Activity of Oral Administered Low Molecular Weight Fucoidan from Laminaria Japonica","volume":"144","author":"Zhao","year":"2016","journal-title":"Thromb. Res."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Pozharitskaya, O.N., Shikov, A.N., Faustova, N.M., Obluchinskaya, E.D., Kosman, V.M., Vuorela, H., and Makarov, V.G. (2018). Pharmacokinetic and Tissue Distribution of Fucoidan from Fucus Vesiculosus after Oral Administration to Rats. Mar. Drugs, 16.","DOI":"10.3390\/md16040132"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Bai, X., Zhang, E., Hu, B., Liang, H., Song, S., and Ji, A. (2020). Study on Absorption Mechanism and Tissue Distribution of Fucoidan. Molecules, 25.","DOI":"10.3390\/molecules25051087"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3390\/md13010048","article-title":"Intestinal Absorption of Fucoidan Extracted from the Brown Seaweed, Cladosiphon Okamuranus","volume":"13","author":"Nagamine","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"419","DOI":"10.3177\/jnsv.63.419","article-title":"Detection of Fucoidan in Urine after Oral Intake of Traditional Japanese Seaweed, Okinawa Mozuku (Cladosiphon Okamuranus Tokida)","volume":"63","author":"Tokita","year":"2017","journal-title":"J. Nutr. Sci. Vitaminol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Kadena, K., Tomori, M., Iha, M., and Nagamine, T. (2018). Absorption Study of Mozuku Fucoidan in Japanese Volunteers. Mar. Drugs, 16.","DOI":"10.3390\/md16080254"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12935-020-01233-8","article-title":"The Anti-Cancer Effects of Fucoidan: A Review of Both in Vivo and in Vitro Investigations","volume":"20","author":"Lin","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Jin, J.-O., Yadav, D., Madhwani, K., Puranik, N., Chavda, V., and Song, M. (2022). Seaweeds in the Oncology Arena: Anti-Cancer Potential of Fucoidan as a Drug-A Review. Molecules, 27.","DOI":"10.3390\/molecules27186032"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Citkowska, A., Szekalska, M., and Winnicka, K. (2019). Possibilities of Fucoidan Utilization in the Development of Pharmaceutical Dosage Forms. Mar. Drugs, 17.","DOI":"10.3390\/md17080458"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Luthuli, S., Wu, S., Cheng, Y., Zheng, X., Wu, M., and Tong, H. (2019). Therapeutic Effects of Fucoidan: A Review on Recent Studies. Mar. Drugs, 17.","DOI":"10.3390\/md17090487"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1089\/jmf.2007.0127","article-title":"Toxicological Evaluation of Fucoidan from Cladosiphon Okamuranus","volume":"11","author":"Gideon","year":"2008","journal-title":"J. Med. Food"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.fct.2004.12.001","article-title":"Toxicological Evaluation of Fucoidan Extracted from Laminaria Japonica in Wistar Rats","volume":"43","author":"Li","year":"2005","journal-title":"Food Chem. Toxicol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1002\/ptr.3138","article-title":"Toxicological Evaluation of Fucoidan from Undaria Pinnatifidain Vitro and in Vivo","volume":"24","author":"Chung","year":"2010","journal-title":"Phytother. Res. PTR"},{"key":"ref_87","first-page":"81","article-title":"Effects of Fucoidan from Fucus Vesiculosus in Reducing Symptoms of Osteoarthritis: A Randomized Placebo-Controlled Trial","volume":"10","author":"Myers","year":"2016","journal-title":"Biol. Targets Ther."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.ijbiomac.2019.10.018","article-title":"Is the Transformation of Fucoidans in Human Body Possible?","volume":"142","author":"Imbs","year":"2020","journal-title":"Int. J. Biol. Macromol."}],"container-title":["Marine Drugs"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-3397\/21\/5\/307\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:38:05Z","timestamp":1760125085000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-3397\/21\/5\/307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,18]]},"references-count":88,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["md21050307"],"URL":"https:\/\/doi.org\/10.3390\/md21050307","relation":{},"ISSN":["1660-3397"],"issn-type":[{"value":"1660-3397","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,18]]}}}