Fucoidan

Rich66 · 12-02-2009, 11:11 PM

How It Works

Bottom Line: Fucoidan has not been shown to treat cancer in humans.

Fucoidan is a complex polysaccharide found in Brown seaweed. It can slow down blood clotting. Laboratory studies suggest that it can prevent growth of cancer cells and also has neuroprotective effects. But there is no human data. Because of its anticoagulant property, fucoidan may increase the side effects of other "blood thinning" drugs.
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Purported Uses

Immunostimulation
Although in vitro data suggests a role for fucoidan in boosting host defense mechanisms, human data is lacking.
Allergies
There is no clinical data to support this use.
Lower blood pressure
This use is not supported by clinical trials.
Decrease cholesterol
There is no data to substantiate this claim.
Inhibit blood clotting
Laboratory studies suggest that Fucoidan has anticoagulant and antithrombotic effects.
Inflammation
There is no data to support this use.
Antibacterial
There is no clinical data to evaluate this use.
Antiviral
No studies have been conducted to investigate this use.

Research Evidence

Laboratory studies are ongoing to determine the antitumor effects of fucoidan. However, there is no data from clinical trials.

Do Not Take If

Theoretically, fucoidan may have additive effects with anticoagulants such as warfarin and heparin.
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Side Effects

No adverse reactions have been reported from use of Fucoidan.
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Common Name

Sulfated alpha-L-fucan
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Clinical Summary

Fucoidan is a sulfated polysaccharide found in the cell walls of many species of Brown seaweed. Preliminary data show that fucoidan has antitumor and antiangiogenic ⁽²⁾ ⁽³⁾ ⁽⁴⁾ ⁽⁵⁾ ⁽⁶⁾ ⁽⁷⁾effects in vitro. These effects are brought about by stimulating natural killer cells and by down regulating AP-I involved in cellular proliferation. Fucoidan also exhibited neuroprotective effects ⁽¹¹⁾ ⁽¹²⁾, but human data is lacking.
In other studies, fucoidan demonstrated anticoagulant ⁽⁸⁾ ⁽⁹⁾ and antithrombotic ⁽¹⁰⁾ activities, and can have additive effects when taken with anticoagulants.
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Food Sources

Several species of Brown seaweed
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Purported uses

Allergies
Bacterial Infections
Hypertension
Immunostimulation
Inflammation
Viral infections

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Constituents

Alpha (1, 2) or Alpha (1, 3) 4-O-sulfated-L-fucose
Galactose
Xylose
Glucoronic acid
⁽¹⁾
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Mechanism of Action

Fucoidan has been shown to inhibit metastasis by preventing adhesion of tumor cells to the extracellular matrix. This is achieved by blocking the fibronectin cell-binding domain, necessary for formation of adhesion complexes ⁽⁴⁾. Fucoidan was also shown to induce apoptosis of human T-cell leukemia virus type I (HTLV-1) that causes Adult T-cell leukemia. It does so by inactivating NF-kB that regulates antiapoptotic proteins. It suppresses AP-I, a transcription factor involved in cellular proliferation and transformation ⁽³⁾. An vitro study showed that Fucoidan can suppress angiogenesis induced by Sarcoma 180 cells in mice ⁽⁵⁾. Fucoidan has immunomodulating effects and enhanced the activity of NK cells, which play a crucial role in mediating tumor cell death ⁽²⁾. The neuroprotective effects of fucoidan are attributed to its ability to suppress tumor necrosis factor-alpha (TNF-alpha)- and interferon-gamma (IFN-gamma)-induced NO production in C6 glioma cells ⁽¹¹⁾ and to its antioxidative effects ⁽¹²⁾.
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Contraindications

Because of its anticoagulant property ⁽⁸⁾ ⁽⁹⁾, fucoidan may have additive effects with anticoagulants such as warfarin and heparin.
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Adverse Reactions

No adverse reactions have been reported from use of Fucoidan.
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References

Giraux JL, Matou S, Bros A, Tapon-Bretaudiere J, Letourneur D, Fischer AM. Modulation of human endothelial cell proliferation and migration by fucoidan and heparin. Eur J Cell Biol 1998; 77(4):352-359.
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(3):245-249.
Haneji K, Matsuda T, Tomita M et al. Fucoidan extracted from cladosiphon okamuranus tokida induces apoptosis of human T-cell leukemia virus type 1-infected T-cell lines and primary adult T-cell leukemia cells. Nutr Cancer 2005; 52(2):189-201.
Liu JM, Bignon J, Haroun-Bouhedja F et al. Inhibitory effect of fucoidan on the adhesion of adenocarcinoma cells to fibronectin. Anticancer Res 2005; 25(3B):2129-2133.
Koyanagi S, Tanigawa N, Nakagawa H, Soeda S, Shimeno H. Oversulfation of fucoidan enhances its anti-angiogenic and antitumor activities. Biochem Pharmacol 2003; 65(2):173-179.
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 Jun;143(6):730-2.
Nagamine T, Hayakawa K, Kusakabe T, et al. Inhibitory effect of fucoidan on Huh7 hepatoma cells through downregulation of CXCL12. Nutr Cancer. 2009;61(3):340-7.
Colliec S, Fischer AM, Tapon-Bretaudiere J, et al. Anticoagulant properties of a fucoïdan fraction. Thromb Res. 1991 Oct 15;64(2):143-54.
Irhimeh MR, Fitton JH, Lowenthal RM. Pilot clinical study to evaluate the anticoagulant activity of fucoidan. Blood Coagul Fibrinolysis. 2009 Aug 18. [Epub ahead of print]
Church FC, Meade JB, Treanor RE, Whinna HC. Antithrombin activity of fucoidan. The interaction of fucoidan with heparin cofactor II, antithrombin III, and thrombin. J Biol Chem. 1989 Feb 25;264(6):3618-23.
Do H, Pyo S, Sohn EH. Suppression of iNOS expression by fucoidan is mediated by regulation of p38 MAPK, JAK/STAT, AP-1 and IRF-1, and depends on up-regulation of scavenger receptor B1 expression in TNF-alpha- and IFN-gamma-stimulated C6 glioma cells. J Nutr Biochem. 2009 Jul 1. [Epub ahead of print]
Luo D, Zhang Q, Wang H, et al. Fucoidan protects against dopaminergic neuron death in vivo and in vitro. Eur J Pharmacol. 2009 Sep 1;617(1-3):33-40.

Rich66 · 12-02-2009, 11:17 PM

J Agric Food Chem. 2009 Sep 23;57(18):8677-82.
Fucoidan induces apoptosis through activation of caspase-8 on human breast cancer MCF-7 cells.

Yamasaki-Miyamoto Y, Yamasaki M, Tachibana H, Yamada K.
Laboratory of Food Chemistry, Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan. yumi_mi_1111@yahoo.co.jp
Fucoidan is an active component of seaweed that has been shown to inhibit proliferation and induce apoptotic cell death in several tumor cells. However, the detailed mechanisms underlying this process have not yet been elucidated. In the present report, we investigated the effect of fucoidan on the induction of apoptosis in human breast cancer MCF-7 cells. Our data demonstrated that fucoidan reduced the viable cell number of MCF-7 cells in a dose- and time-dependent manner. In contrast, fucoidan did not affect the viable cell number of normal human mammary epithelial cells. Results from the apoptosis assay demonstrated that fucoidan induced internucleosomal DNA fragmentation, chromatin condensation, activation of caspase-7, -8, and -9, and cleavage of poly(ADP ribose) polymerase. Furthermore, expression of Bid was decreased, whereas truncated Bid was increased by fucoidan treatment. There was also a decline in cytosolic Bax and a striking increase of cytosolic cytochrome c. Caspase-8-specific inhibitor, z-ITED-fmk, canceled the cytotoxicity of fucoidan, activation of caspase-7, -8, and -9, and a series of changes in Bax, Bid, and cytochrome c. However, caspase-9-specific inhibitor exerted a moderate inhibitory effect on the cytotoxicity of fucoidan. These data indicated that fucoidan could induce apoptotic cell death through a caspase-8-dependent pathway in MCF-7 cells.

PMID: 19754176 [PubMed - in process]

Int J Oncol. 2009 Nov;35(5):1183-9.
Fucoidan-Vitamin C complex suppresses tumor invasion through the basement membrane, with scarce injuries to normal or tumor cells, via decreases in oxidative stress and matrix metalloproteinases.

Saitoh Y, Nagai Y, Miwa N.
Cell-Death Control BioTechnology Laboratory, Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, Shobara, Hiroshima 727-0023, Japan.
Fucoidan (Fucdn) and vitamin C (VC) were saturatedly dissolved in water and lyophilized and thoroughly ethanol-rinsed until no detection for supernatant vitamin C to form the Fucdn-VC (1:0.23 wt/wt) inclusion body (Fucdn-VC-IB). Fucdn-VC-IB increased not only VC-stabilizing at 37 degrees C, but also hydroxyl-radical scavenging as shown by ESR/spin-trap method, more markedly than a mere mixture of Fucdn:VC (1:0.23 wt/wt). Invasion of human fibrosarcoma cells HT-1080 through the basement membrane was repressed by Fucdn-VC-IB of non-cytotoxic concentrations without significant inhibition to human skin dermal fibroblasts DUMS-16 cells. Fucdn-VC-IB suppressed the invasiveness-related gelatinases MMP-2/9, and diminished reactive oxygen species inside the cytoplasm around the nucleus, in HT-1080 cells as shown by electrophoretic zymography and the redox indicator NBT assay, respectively. Thus Fucdn-VC-IB markedly exhibits antioxidant and MMP-suppressing activities and preferentially inhibited tumor invasion without cytotoxicity to normal cells, and is suggested as a potent tumor-invasion suppressor.

PMID: 19787274 [PubMed - indexed for MEDLINE]

Biol Pharm Bull. 2009 Oct;32(10):1760-4.

Apoptosis inducing activity of fucoidan in HCT-15 colon carcinoma cells.

Hyun JH, Kim SC, Kang JI, Kim MK, Boo HJ, Kwon JM, Koh YS, Hyun JW, Park DB, Yoo ES, Kang HK.
School of Medicine, Institute of Medical Sciences, Jeju National University, South Kore.
The antitumor activity of fucoidan from Fucus vesiculosus was investigated in human colon carcinoma cells. The crude fucoidan, a polysaccharide composed predominantly of sulfated fucose, markedly inhibited the growth of HCT-15 cells (human colon carcinoma cells). After HCT-15 cells were treated with fucoidan, several apoptotic events such as DNA fragmentation, chromatin condensation and increase of the population of sub-G1 hypodiploid cells were observed. In the mechanism of fucoidan-induced apoptosis, we examined changes in Bcl-2 and Bax protein expression levels and activation of caspases. Fucoidan decreased Bcl-2 expression, whereas the expression of Bax was increased in a time-dependent manner compared to the control. In addition, the active forms of caspase-9 and caspase-3 were increased, and the cleavage of poly(ADP-ribose) polymerase (PARP), a vital substrate of effector caspase, was observed. Furthermore, the induction of apoptosis was also accompanied by a strong activation of extracellular signal-regulated kinase (ERK) and p38 kinase and an inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt in a time-dependent manner. These findings provide evidence demonstrating that the pro-apoptotic effect of fucoidan is mediated through the activation of ERK, p38 and the blocking of the PI3K/Akt signal pathway in HCT-15 cells. These data support the hypothesis that fucoidan may have potential in colon cancer treatment.

PMID: 19801840 [PubMed - in process]

Bull Exp Biol Med. 2007 Jun;143(6):730-2.
Antitumor and antimetastatic activity of fucoidan, a sulfated polysaccharide isolated from the Okhotsk Sea Fucus evanescens brown alga.

[Article in English, Russian]
Alekseyenko TV, Zhanayeva SY, Venediktova AA, Zvyagintseva TN, Kuznetsova TA, Besednova NN, Korolenko TA.
Institute of Physiology, Siberian Division of Russian Academy of Medical Sciences, Novosibirsk.
Antitumor and antimetastatic activities of fucoidan, a sulfated polysaccharide isolated from Fucus evanescens (brown alga in Okhotsk sea), was studied in C57Bl/6 mice with transplanted Lewis lung adenocarcinoma. Fucoidan after single and repeated administration in a dose of 10 mg/kg produced moderate antitumor and antimetastatic effects and potentiated the antimetastatic, but not antitumor activities of cyclophosphamide. Fucoidan in a dose of 25 mg/kg potentiated the toxic effect of cyclophosphamide.

PMID: 18239813 [PubMed - indexed for MEDLINE]