Fucoidan

What is Fucoidan?

Fucoidan is a type of sulfated polysaccharide that is found in the cell walls of several different species of brown seaweed, including bladderwrack and kelp.  It contains galactose, glucoronic acid, xylose and several other major constituents that give the substance its potential health benefits allowing it to be used medicinally for a wide variety of health purposes including: lowering blood pressure, lowering cholesterol, treating infections, helping with arthritis pain and relieving allergies.  Fucoidan has also been found to have significant immune-boosting effects and has shown effectiveness in cases involving meningitis.

The anti-Cancer benefits of Fucoidan

Fucoidan also appears to have anti-tumor, anti-cancer and neuroprotective actions as well according to the Memorial Sloan-Kettering Cancer Center. More specifically, the compound acts to block cancer cells from developing and growing.  The substance also offers actions that help to modulate the immune system and antioxidant qualities as well.  Seaweeds containing fucoidan have been found to have anti-tumor activity in mice, and Japanese researchers at the Biomedical Research Laboratories have found that Fucoidan caused leukemia, lymphoma, colorectal and stomach cancer cells to self-destruct.

Studies of Fucoidan for various cancers

Breast Cancer- For this study, breast cancer cells taken from a mouse were exposed to fucoidan to investigate the relationship between fucoidan and the Wnt/β-catenin signaling pathway in vivo and in vitro. We found that fucoidan significantly inhibited cell growth, increased cell death, and induced G1 cell cycle arrest in 4T1 cells. Fucoidan also reduced β-catenin expression and T cell factor/lymphoid-enhancing factor reporter activity. Furthermore, it downregulated the expression of downstream target genes such as c-myc, cyclin D1, and survivin. Intraperitoneal injection of fucoidan in tumor-bearing mice reduced the tumor volume and weight. Fucoidan induced aberrant downregulation of β-catenin in tumor tissues with a significant increase in apoptosis. Thus, our data suggested that exerts its anticancer activity through downregulation of Wnt/β-catenin signaling. Fucoidan may be an effective therapy for the chemo-prevention and treatment of mouse breast cancer. Link to study

Lung Cancer–  Recently there has been an increased interest in the pharmacologically active natural products associated with remedies of various kinds of diseases, including cancer. Fucoidan is a polysaccharide derived from brown seaweeds and has long been used as an ingredient in some dietary supplement products. Although fucoidan has been known to have anti-cancer activity, the anti-metastatic effects and its detailed mechanism of actions have been poorly understood. Therefore, the aims of this study were to demonstrate the anti-metastatic functions of fucoidan and its mechanism of action using A549, a highly metastatic human lung cancer cell line.  Fucoidan inhibits the growth of A549 cells at the concentration of 400 µg/ml. Fucoidan treatment of non-toxic dose (0-200 µg/ml) exhibits a concentration-dependent inhibitory effect on the invasion and migration of the cancer cell via decreasing its MMP-2 activity. To know the mechanism of these inhibitory effects, Western blotting was performed. Fucoidan treatment down-regulates extracellular signal-related kinase 1 and 2 (ERK1/2) and phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin (PI3K-Akt-mTOR) pathways. Furthermore, fucoidan decreases the cytosolic and nuclear levels of Nuclear Factor-kappa B (p65).  The present study suggests that fucoidan exhibits anti-metastatic effect on A549 lung.  Link to study

Leukemia–  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. 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. An vitro study showed that Fucoidan can suppress angiogenesis induced by Sarcoma 180 cells in mice. Fucoidan has immunomodulating effects and enhanced the activity of NK cells, which play a crucial role in mediating tumor cell death. 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  and to its antioxidative effects.  Link to article

Lymphoma – Seaweed extract may eventually emerge as a lymphoma treatment, according to laboratory research presented at the second AACR Dead Sea International Conference on Advances in Lymphoma is a cancer of the immune system and is classified into Hodgkin’s and non-Hodgkin’s types, which are then further classified into B-cell and T-cell groups.   “Some forms of B-cell lymphoma are especially resistant to standard treatment and thus new therapies are needed,” said Mohammad Irhimeh, Ph.D., assistant professor of hematoncology and stem cells at the Hashemite University in Jordan. “In this study, we looked at a new treatment strategy using novel active compounds derived from a natural source — seaweed.”  Seaweeds containing fucoidan, a sulfated polysaccharide similar to heparin in chemical structure, have been reported to have anti-tumor activity in mice and some cell lines.  For the study, Irhimeh and colleagues at the University of California, Berkeley, and Royal Hobart Hospital in Australia treated lymphoma cell lines with a commercially available seaweed extract.  They found that the extract had an inhibitory effect on the growth of lymphoma cell lines, while leaving the control healthy cells intact. The researchers also noted a significant pattern of activity in the genes known to be linked with apoptosis, or cell death, in lymphoma. Irhimeh said they would continue to study the mechanism of action for these biological effects and had a goal of conducting phase II or III clinical trials. Source article

Bile Duct Cancers –  The current study examined the anti-tumor effects of fucoidan extracted from Okinawa mozuku on 15 human cell lines (6 hepatocellular carcinomas, 1 cholangiocarcinoma, 1 gallbladder cancer, 2 ovarian cancers, 1 hepatoblastoma, 1 neuroblastoma and 3 renal cancers) using an MTT assay. Changes in apoptosis and the cell cycle were analyzed by flow cytometry. The results revealed that cell proliferation was suppressed in 13 cell lines in a time- and/or dose-dependent manner; this suppression was marked in the hepatocellular carcinoma, cholangiocarcinoma and gallbladder carcinoma cell lines. In contrast, proliferation of the neuroblastoma and 1 of the 2 ovarian carcinoma cell lines was not affected. The ratio of apoptotic cells significantly increased in 5 of the 6 hepatocellular carcinoma cell lines, and the ratio of G2/M cells increased in the 3 hepatocellular cell lines examined. These observations indicate that fucoidan is a potential anti-tumor agent for the treatment of bile duct cancers, such as hepatocellular carcinoma, cholangiocarcinoma and gall-bladder carcinoma. Link to Study

Prostate Cancer- The present study examined the anti-cancer effect of fucoidan obtained from Undaria pinnatifida in PC-3 cells, human prostate cancer cells. Fucoidan induced the apoptosis of PC-3 cells by activating both intrinsic and extrinsic pathways. The induction of apoptosis was accompanied by the activation of extracellular signal-regulated kinase mitogen-activated protein kinase (ERK1/2 MAPK) and the inactivation of p38 MAPK and phosphatidylinositol 3-kinase (PI3K)/Akt. In addition, fucoidan also induced the up-regulation of p21Cip1/Waf and down-regulation of E2F-1 cell-cycle-related proteins. Furthermore, in the Wnt/β-catenin pathway, fucoidan activated GSK-3β that resulted in the decrease of β-catenin level, followed by the decrease of c-myc and cyclin D1 expressions, target genes of β-catenin in PC-3 cells. These results suggested that fucoidan treatment could induce intrinsic and extrinsic apoptosis pathways via the activation of ERK1/2 MAPK, the inactivation of p38 MAPK and PI3K/Akt signaling pathway, and the down-regulation of Wnt/β-catenin signaling pathway in PC-3 prostate cancer cells. These data support that fucoidan might have potential for the treatment of prostate cancer. Link to study

More Studies-  In this study, the anticancer activity of the fucoidan extracted from the brown seaweed Undaria pinnatifida was investigated in human hepatocellular carcinoma SMMC-7721 cells, and the underlying mechanisms of action were investigated. SMMC-7721 cells exposed to fucoidan displayed growth inhibition and several typical features of apoptotic cells, such as chromatin condensation and marginalization, a decrease in the number of mitochondria, and in mitochondrial swelling and vacuolation. Fucoidan-induced cell death was associated with depletion of reduced glutathione (GSH), accumulation of high intracellular levels of reactive oxygen species (ROS), and accompanied by damage to the mitochondrial ultrastructure, depolarization of the mitochondrial membrane potential (MMP, Δψm) and caspase activation. Moreover, fucoidan led to altered expression of factors related to apoptosis, including downregulating Livin and XIAP mRNA, which are members of the inhibitor of apoptotic protein (IAP) family, and increased the Bax-to-Bcl-2 ratio. These findings suggest that fucoidan isolated from U. pinnatifida induced apoptosis in SMMC-7721 cells via the ROS-mediated mitochondrial pathway.  Link studies

Link to more studies on fucoidan available through PubMed

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