Fucoidan aus Braunalgen

Bettina Hees

doi:10.1055/a-1615-0382

Deutsche Zeitschrift für Onkologie, Table of Contents

Deutsche Zeitschrift für Onkologie 2021; 53(04): 148-156
DOI: 10.1055/a-1615-0382

Forschung

Fucoidan aus Braunalgen

Neuer Wirkstoff aus dem Meer für die komplementäre TumortherapieFucoidan from Brown Algae New Active Substance from the Sea for Complementary Tumor Therapy

Bettina Hees

¹MMR Medical Marine Research

› Author Affiliations

Abstract

Zusammenfassung

Fucoidan ist ein Polysaccharid, das in Meeresbraunalgen, vor allem der Wakame-Alge, vorkommt. Es ist in vielen Ländern Asiens Bestandteil der täglichen Ernährung mit Algen, darüber hinaus wird es in der traditionellen asiatischen Medizin zur komplementären Behandlung von Tumorerkrankungen eingesetzt. Seit Kurzem ist Fucoidan auch in der EU als „Novel Food“-Lebensmittel bzw. Nahrungsergänzung zugelassen. Fucoidane besitzen eine Vielzahl an antikanzerogenen Wirkungen, was in vitro, in vivo und in klinischen Pilotstudien nachgewiesen werden konnte: Sie reduzieren proinflammatorische Prozesse, können die Proliferation von Krebszellen unterdrücken, aktivieren die Apoptose-Signale von Krebszellen und hemmen die Bildung von vaskulären Wachstumsfaktoren (VEGF), wodurch Angiogenese und Metastasierung unterdrückt werden können. Fucoidan besitzt sowohl systemische Wirkungen – erstmalig nachgewiesen mit Hilfe der microRNA Biomarker-Diagnostik – als auch lokale Wirkungen. Als Biological Response Modifier aktiviert und verbessert Fucoidan die Immunantwort im Darm als First-Line-Abwehr von Tumorzellen und Schlüsselfaktor der Tumorbekämpfung, es wirkt zusätzlich als Booster der natürlichen Killerzellaktivität. Fucoidan kann die Nebenwirkungen von Chemo- und Strahlentherapien reduzieren und es kann die therapeutischen Effekte konventioneller Tumortherapien verbessern. Der Beitrag stellt klinische Ergebnisse zu Fucoidan beim metastasierten Kolonkarzinom sowie bei Brustkrebs vor.

Abstract

Fucoidan is a polysaccharide found in marine brown algae, especially wakame algae. It is part of the daily diet of algae in many Asian countries, in addition, it is used in traditional Asian medicine for the complementary treatment of tumor diseases. Recently, fucoidan has also been approved in the EU as a “novel food”. Fucoidans possess a variety of anticarcinogenic effects, which has been demonstrated in vitro, in vivo and in pilot clinical studies: They reduce proinflammatory processes, can suppress cancer cell proliferation, activate cancer cell apoptosis signaling, and inhibit vascular growth factor (VEGF) formation, thereby suppressing angiogenesis and metastasis. Fucoidan has both, systemic effects – demonstrated for the first time using microRNA biomarker diagnostics – and local effects. As a biological response modifier, fucoidan activates and enhances the immune response in the intestine as a first line of defense against tumor cells and a key factor in tumor control, it also acts as a booster of natural killer cell activity. Fucoidan can reduce the side effects of chemotherapy and radiotherapy and it can improve the therapeutic effects of conventional tumor therapies. The paper presents clinical results on fucoidan in metastatic colon carcinoma and breast cancer.

Schlüsselwörter

Fucoidan - Undaria pinnatifida - komplementäre Tumortherapie - Braunalgen - Brustkrebs

Key words

Fucoidan - Undaria pinnatifida - complementary tumor therapy - brown seaweed - breast cancer

Full Text

References

Literatur
1 Trejo-Avila LM. et al In vitro anti-canine distemper virus activity of fucoidan extracted from the brown alga Cladosiphon okamuranus. VirusDisease 2014; 25: 474-480
2 Besednova NN, Zaporozhets TS, Somova LM. et al Review: prospects for the use of extracts and polysaccharides from marine algae to prevent and treat the diseases caused by Helicobacter pylori. Helicobacter 2015; 20: 89-97
3 Lean QY, Eri RD, Fitton JH. et al Fucoidan extracts ameliorate acute colitis. PLoS One 2015; 10: e0128453
4 Thakur V. et al The natural compound fucoidan from New Zealand Undaria pinnatifida synergizes with the ERBB inhibitor lapatinib enhancing melanoma growth inhibition. Oncotarget 2017; 8: 17887-17896
5 Fitton J. Therapies from fucoidan; multifunctional marine polymers. Marine Drugs 2011; 9: 1731-1760
6 Teas J. et al Dietary seaweed (Laminaria) and mammary carcinogenesis in rats. Cancer Res 1984; 44: 2758-2761
7 Coombe DR. et al Analysis of the inhibition of tumour metastasis by sulphated polysaccharides. Int J Cancer 1987; 39: 82-88
8 Irhimeh MR. et al A quantitative method to detect fucoidan in human plasma using a novel antibody. Methods Find Exp Clin Pharmacol 2005; 27: 705-710
9 Tokita Y. et al Development of a fucoidan-specific antibody and measurement of fucoidan in serum and urine by sandwhich ELISA. Biosci Biotechnol Biochem 2010; 74: 350-357
10 Maruyama H, Tamauchi H, Hashimoto M, Nakano T. Antitumor activity and immune response of Mekabu fucoidan extracted from sporophyll of Undaria pinnatifida. In Vivo 2003; 17: 245-249
11 Koyanagi S, Tanigawa N, Nakagawa H. et al Oversulfation of fucoidan enhances its anti-angiogenic and antitumor activities. Biochem Pharmacol 2003; 65: 173-179
12 Zugmaier G, Favoni R, Jaeger R. et al Polysulfated heparinoids selectively inactivate heparin-binding angiogenesis factors. Ann N Y Acad Sci 1999; 886: 243-248
13 Fitton JH, Stringer DN, Karpiniec SS. Therapies from fucoidan: An update. Mar Drugs 2015; 13: 5920-5946
14 Kwak JY. Fucoidan as a marine anticancer agent in preclinical development. Mar Drugs 2014; 12: 851-870
15 Atashrazm F. et al Fucoidan and cancer: a multifunctional molecule with anti-tumor potential. Mar Drugs 2015; 13: 2327-2346
16 Kim EJ. et al Fucoidan present in brown algae induces apoptosis of human colon cancer cells. BMC Gastroenterology 2010; 10: 96
17 Yamasaki-Miyamoto Y, Yamasaki M, Tachibana H. et al Fucoidan induces apoptosis through avtivation of caspase-8 on human breast cancer MCF-7 cells. J Agric Food Chem 2009; 57: 8677-8682
18 Aisa Y. et al Fucoidan induces apoptosis of human HS-sultan cells accompanied by activation of caspase-3 and down-regulation of ERK pathways. Am J Hematol 2005; 78: 7-14
19 Hanssen HP. Makroalgen – Potenzial für Pharmazie und Kosmetik. DAZ 2010; 150: 74
20 Atashrazm F. et al Fucoidan and cancer: a multifunctional molecule with anti-tumor potential. Mar Drugs 2015; 13: 2327-2346
21 Itoh H, Noda H, Amano H. et al Antitumor activity and immunological properties of marine algal polysaccharides, especially fucoidan, prepared from Sargassum thunbergii of Phaeophyceae. Anticancer Res 1993; 13: 2045-2052
22 Sun J, Song B, Zhang L. et al Fucoidan inhibits CCL22 production through NF-kappaB pathway in M2 macrophages: a potential therapeutic strategy for cancer. Sci Rep 2016; 6: 35855
23 Sweeney EA. et al Sulfated polysaccharides increase plasma levels of SDF-1 in monkeys and mice: involvement in mobilization of stem/progenitor cells. Blood 2002; 99: 44-51
24 Fermas S. et al Sulfated oligosaccharides (heparin and fucoidan) binding and dimerization of stromal cell-derived factor-1 (SDF-1/CXCL 12) are coupled as evidenced by affinity CE-MS analysis. Glycobiology 2008; 18: 1054-1064
25 Kwak JY. Fucoidan as a marine anticancer agent in preclinical development. Mar Drugs 2014; 12: 851-870
26 Link AR. et al Use of self-care and practitioner-based forms of complementary and alternative medicine before and after a diagnosis of breast cancer. Evid Based Complement Alternat Med 2013; 2013: 301549
27 Burney M, Mathew L, Gaikwad A. et al Evaluation fucoidan extracts from Undaria pinnatifida and Fucus vesiculosus in combination with anticancer drugs in human cancer orthotopic mouse models. Integr Cancer Ther 2018; 17: 755-761
28 Tocaciu S, Oliver LJ, Lowenthal RM. et al The effect of Undaria pinnatifida fucoidan on the pharmacokinetics of letrozole and tamoxifen in patients with breast cancer. Integr Cancer Ther 2018; 17: 99-105
29 Chen MC, Hsu WL, Hwang PA. et al Combined administration of fucoidan ameliorates tumor and chemotherapy-induced skeletal muscle atrophy in bladder cancer-bearing mice. Oncotarget 2016; 7: 51608-51618
30 Tokita Y, Nakajima K, Mochida H. et al Development of a fucoidan-specific antibody and measurement of fucoidan in serum and urine by sandwich ELISA. Biosci Biotechnol Biochem 2010; 74: 350-357
31 Michel C. et al In vitro fermentation by human faecal bacteria of total and purified dietary fibres from brown seaweeds. Br J Nutr 1996; 75: 263-280
32 Boisson-Vidal C. et al Relationship between antithrombotic activities of fucans and their structure. Drug Development Research 2000; 51: 216-224
33 Holtkamp AD. Isolation, Characterization, Modification and Application of Fucoidan from Fucus vesiculosus [PhD Thesis] Technische Universität Braunschweig. 2009
34 Holtkamp AD, Kelly S, Ulber R, Lang S. Fucoidans and fucoidanases--focus on techniques for molecular structure elucidation and modification of marine polysaccharides. Appl Microbiol Biotechnol 2009; 82: 1-11
35 Bui ML. et al Studies on fucoidan and its production from Vietnamese brown seaweeds. ASEAN J Sci Technol Develop 2005; 22: 371-380
36 Ajisaka K, Agawa S, Nagumo S. et al Evaluation and comparison of the antioxidative potency of various carbohydrates using different methods. J Agric Food Chem 2009; 57: 3102-3107
37 Wang J. et al Potential antioxidant and anticoagulant capacity of low molecular weight fucoidan fractions extracted from Laminaria japonica. Int J Biol Macromol 2010; 46: 6-12
38 Tokita Y, Nakajima K, Mochida H. et al Development of a fucoidan-specifc antibody and measurement of fucoidan in serum and urine by sandwich ELISA. Biosci Biotechnol Biochem 2010; 74: 350-357
39 Nagamine T, Nakazato K, Tomioka S. et al Intestinal absorption of fucoidan extracted from the brown seaweed Cladosiphon okamuranus. Mar Drugs 2014; 13: 48-64
40 Kadena K, Tomori M, Iha M, Nagamine T. Absorption study of Mozuku Fucoidan in Japanese volunteers. Mar Drugs 2018; 16: 254
41 Huheihel M, Ishanu V, Tal J, Arad SM. Activity of Porphyridium sp. polysaccharide against Herpes simplex viruses in vitro and in vivo. J Biochem Biophys Methods 2002; 50: 189-200
42 Alekseyenko TV, Zhanayeva SY, Venediktova AA. et al Antitumor and antimetastatic activity of fucoidan, a sulfated polysaccharide isolated from the Okhotsk Sea Fucus evanescens brown alga. Bull Exp Biol Med 2007; 143: 730-732
43 Huang TH, Chiu YH, Chan YL. et al Prophylactic administration of fucoidan represses cancer metastasis by inhibiting vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) in Lewis tumor-bearing mice. Mar Drugs 2015; 13: 1882-1900
44 Koyanagi S, Tanigawa N, Nakagawa H. et al Oversulfation of fucoidan enhances its anti-angiogenic and antitumor activities. Biochem Pharmacol 2003; 65: 173-179
45 Rui X, Pan HF, Shao SL, Xu XM. Anti-tumor and anti-angiogenic effects of fucoidan on prostate cancer: possible JAK-STAT3 pathway. BMC Complement Altern Med 2017; 17: 378
46 Tsai HL, Tai CJ, Huang CW. et al Efficacy of low-molecular-weight fucoidan as a supplemental therapy in metastatic colorectal cancer patients: a double-blind randomized controlled trial. Mar Drugs 2017; 15: 122
47 Garcia-Vaquero M, Rajauria G, O’Doherty JV, Sweeney T. Polysaccharides from macroalgae: Recent advances, innovative technologies and challenges in extraction and purification. Food Res Int 2017; 99: 1011-1020
48 Shannon E, Conlon M, Hayes M. Seaweed components as potential modulators of the gut microbiota. Mar Drugs 2021; 19: 358
49 Su CM, Wang MY, Hong CC. et al miR-520h is crucial for DAPK2 regulation and breast cancer progression. Oncogene 2016; 35: 1134-1142
50 Mori MA, Ludwig RG, Garcia-Martin R. et al Extracellular miRNAs: From biomarkers to mediators of physiology and disease. Cell Metab 2019; 30: 656-673
51 Cui J, Zhou B, Ross SA, Zempleni J. Nutrition, microRNAs, and human health. Adv Nutr 2017; 8: 105-112
52 Yan MD, Yao CJ, Chow JM. et al Fucoidan elevates microRNA-29b to regulate DNMT3B-MTSS1 axis and inhibit EMT in human hepatocellular carcinoma cells. Mar Drugs 2015; 13: 6099-6116
53 Wu SY, Wu AT, Yuan KS. et al Brown seaweed fucoidan inhibits cancer progression by dual regulation of mir-29c/ADAM12 and miR-17-5p/PTEN axes in human breast cancer cells. J Cancer 2016; 7: 2408-2419
54 https://flexikon.doccheck.com/de/PI3K/Akt-Signalweg
55 Hsu HY, Lin TY, Hwang PA. et al Fucoidan induces changes in the epithelial to mesenchymal transition and decreases metastasis by enhancing ubiquitin-dependent TGFbeta receptor degradation in breast cancer. Carcinogenesis 2013; 34: 874-884
56 Gueven N, Spring KJ, Holmes S. et al Micro RNA expression after ingestion of fucoidan; a clinical study. Mar Drugs 2020; 18: 143
57 Tokita Y, Nakajima K, Mochida H. et al Development of a fucoidan-specific antibody and measurement of fucoidan in serum and urine by sandwich ELISA. Biosci Biotechnol Biochem 2010; 74: 350
58 Lowenthal RM, Fitton JH. Are seaweed-derived fucoidans possible future anti-cancer agents?. J Applied Phycology 2015; 27: 2075-2077
59 Mathew LB. et al Preclinical evaluation of safety of fucoidan extracts from Undaria pinnatifida and Fucus vesiculosus for use in cancer treatment. Integr Cancer Ther 2017; 16: 572-584
60 Myers SP, O'Connor J, Fitton JH. et al A combined phase I and II open label study on the effects of a seaweed extract nutrient complex on osteoarthritis. Biologics 2010; 4: 33-44
61 Irhimeh MR, Fitton JH, Lowenthal RM. Fucoidan ingestion increases the expression of CXCR4 on human CD34+ cells. Exp Hematol 2007; 35: 989-994
62 Myers SP, Mulder AM, Baker DG. et al Effects of fucoidan from Fucus vesikulosus in reducing symptoms of osteoarthitis: a randomized placebo-controlled trial. Biologics 2016; 10: 81-88
63 Irhimeh MR, Fitton JH, Lowenthal RM. Pilot clinical study to evaluate the anticoagulant activity of fucoidan. Blood Coagul Fibrinolysis 2009; 20: 607-610
64 https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32018R1023&from=EN
65 Gassmann P, Kang ML, Mees ST, Haler J. In vivo tumor cell adhesion in the pulmonary microvasculature is exclusively mediated by tumor cell-endothelial cell interaction. BMC Cancer 2010; 10: 177
66 Takahashi H. et al An exploratory study on the anti-inflammatory effects of fucoidan in relation to quality of life in advanced cancer patients. Integr Cancer Ther 2018; 17: 282-291
67 Larson SJ, Dunn AJ. Behavioral effects of cytokines. Brain Behav Immun 2001; 15: 371-387
68 Gasiorowska A. et al Subclinical inflammation and endothelial dysfunction in patients with chronic pancreatitis and newly diagnosed pancreatic cancer. Dig Dis Sci 2016; 61: 1121-1129
69 Ellebæk MB. et al Cytokine response in peripheral blood indicates different pathophysiological mechanisms behind anastomotic leakage after low anterior resection: a pilot study. Tech Coloproctol 2014; 18: 1067-1074
70 Qian N, Chen X, Han S. et al Circulating IL-1beta levels, polymorphisms of IL-1β, and risk of cervical cancer in Chinese women. J Cancer Res Clin Oncol 2010; 136: 709-716
71 Dinarello CA. Why not treat human cancer with interleukin-1 blockade?. Cancer Metastasis Rev 2010; 29: 317-329
72 Scheede-Bergdahl C. et al Is IL-6 the best pro-inflammatory biomarker of clinical outcomes of cancer cachexia?. Clin Nutr 2012; 31: 85-88
73 Balkwill FR, Mantovani A. Cancer-related inflammation: common themes and therapeutic opportunities. Semin Cancer Biol 2012; 22: 33-40
74 Lesovaya E. et al Discovery of compound A: a selective activator of the glucocorticoid receptor with anti-inflammatory and anti-cancer activity. Oncotarget 2015; 6: 30730-30744
75 Lau PM, Stewart K, Dooley M. The ten most common adverse drug reactions (ADRs) in oncology patients: do they matter to you?. Support Care Cancer 2004; 12: 626-633
76 Lanas A, Hunt R. Prevention of anti-inflammatory drug-induced gastrointestinal damage: benefits and risks of therapeutic strategies. Ann Med 2006; 38: 415-428
77 Coussens LM, Zitvogel L, Palucka AK. Neutralizing tumor-promoting chronic inflammation: a magic bullet?. Science 2013; 339: 286-291
78 Ikeguchi M, Yamamoto M, Arai Y. et al Fucoidan reduces the toxicities of chemotherapy for patients with unresectable advanced or recurrent colorectal cancer. Oncol Lett 2011; 2: 319-322
79 Iop A, Manfredi AM, Bonura S. Fatigue in cancer patients receiving chemotherapy: an analysis of published studies. Ann Oncol 2004; 15: 712-720
80 Novoyatleva T, Schermuly RT. et al Evidence for Fucoidan-p-selectin axis as a therapeutic target on hypoxia-induced pulmonary hypertension. Am J Respir Crit Care Med 2019; 199: 1407-1420
81 https://www.uni-giessen.de/ueber-uns/pressestelle/pm/pm04-19
82 https://ec.europa.eu/regional_policy/de/projects/Germany/the-healing-powers-of-brown-algae-investigated-in-danish-german-project
83 Li B, Lu F, Wei X, Zhao R. Fucoidan: structure and bioactivity. Molecules 2008; 13: 1671-1695
84 Zhang Z, Teruya K, Yoshida T. et al Fucoidan extract enhances the anti-cancer activity of chemotherapeutic agents in MDA-MB-231 and MCF-7 breast cancer cells. Mar Drugs 2013; 11: 81-98
85 Ale MT, Maruyama H, Tamauchi H. et al 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. Int J Biol Macromol 2011; 49: 331-336
86 Azuma K, Ishihara T, Nakamoto H. et al Effects of oral administration of fucoidan extracted from Cladosiphon okamuranus on tumor growth and survival time in a tumor-bearing mouse model. Mar Drugs 2012; 10: 2337-2348