Glyconutrients

Rupture of abdominal aortic aneurysm (AAA) is one of the leading causes of sudden death among the elderly. Most incidental AAAs are below the threshold for intervention at the time of detection; however, there is no evidence that commonly used cardiovascular drugs have clinical beneficial effects on AAA progression. Therefore, in addition to current cardiovascular risk-reducing treatments, an adjunctive medical therapy targeting the regulation of extracellular matrix metabolism is still required in the clinical setting.

Background Radioiodine (RI) treatments can destroy the cellular components of salivary glands (SG) and disrupt their function. This study investigated whether fucoidan could attenuate radioiodine-induced SG dysfunction in a mouse model. Methods Female C57BL/6 mice (n = 36) were classified into three groups; i) a normal (control) group, ii) an RI-treated group (0.2 mCi/20 g mouse, administered orally), and iii) a fucoidan and RI-treated group. Mice in each group were classified into three subgroups and sacrificed at 2, 4, and 12 weeks after RI treatment. The measurements of salivary flow rates and lag times and histomorphologic examinations were performed, and apoptotic assays were conducted. Changes in salivary 99mTechnetium (Tc)-pertechnetate parameters using single-photon emission computed tomography were followed. Results Salivary flow rates and lag times in the fucoidan group were improved compared to the RI-treated group. Histologic examinations of SGs in the fucoidan group showed mucin-rich parenchymal areas and reduced periductal fibrosis as compared to the RI-treated group. Moreover, compared with the RI-treated group, fucoidan-treated groups showed evidence of cytoprotection, with a greater number of salivary epithelial cells and myoepithelial cells being observed. Fewer apoptotic cells were observed in the fucoidan group as compared to the RI group. The extent of 99mTc pertechnetate excretion in the fucoidan group was similar to that of the control group. Conclusion Our results demonstrate that fucoidan administration before RI treatment could attenuate RI-induced SG damage and provides a possible candidate for preventing SG damage induced by RI.

Marine organisms are sources of several natural compounds with potential clinical use. However, only a few marine-based pharmaceuticals have been approved for use due to limited knowledge on their biological activities. Here, we identified the functional role of fucoidan extracted from Fucus vesiculosus on ovarian cancer. Fucoidan increased the death of ES-2 and OV-90 cells, through a reduction in proliferation, cell cycle arrest, releases of cytochrome c, reactive oxygen species (ROS) generation, and endoplasmic reticulum (ER) stress. Additionally, fucoidan increased the concentration of cytosolic and mitochondrial calcium in both cells. The decrease of cell proliferation was controlled by the inactivation of PI3K and MAPK signaling cascades in ES-2 and OV-90 cells. In a toxicity assay with normal zebrafish larvae, fucoidan did not induce toxicity, cardiotoxicity, development, kinesis, and apoptosis at different concentrations. However, it disrupted tumor formation and vascular development in a zebrafish xenograft model and angiogenesis transgenic (Tg, fli1-eGFP) model, respectively. Collectively, the results indicate that fucoidan may be a novel pharmaceutical for the management of human ovarian cancer.

Fucoidan, a sulfated polysaccharide present in brown seaweed, has demonstrated anticancer activity in lung, breast, liver and colon cells. The insulin-like growth factor (IGF) signaling pathway regulates growth in HT-29 cells through the insulin receptor substrate-1 (IRS-1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Ras/Raf/extracellular signal-regulated kinase (ERK) pathways. The aim of the present study was to investigate whether fucoidan downregulates the IGF-IR signaling pathway in HT-29 human colon cancer cells. Fucoidan treatment (0-1,000 µg/ml) was administered for 24 h in HT-29 cells. First, we investigated IRS-1/PI3K/AKT pathway-related protein expression levels following treatment with fucoidan (0-500 µg/ml) using western blot analysis. Fucoidan significantly inhibited the expression of IGF-IR, PTEN, PI3K and AKT as well as their phosphorylated forms (p-IRS-1, p-PI3K and p-AKT). Next, we investigated the effects of fucoidan on Ras/Raf/ERK pathway‑related protein expression levels in HT-29 cells. Fucoidan significantly inhibited the expression of IGF-IR, Shc, Ras, SOS, Raf and MEK. HT-29 cells were then incubated in the presence of fucoidan (0 or 250 µg/ml), and IGF-I (10 nM) was added for 0 to 60 min. Immunoprecipitation (IP) experiments showed that fucoidan inhibited IGF-I-induced phosphorylation of IGF-IR, PI3K, Shc (IP, IGF-IR), and phosphorylated IRS-1 and PI3K (IP, IRS-1) compared to the control group. Western blot analysis showed that fucoidan inhibited the expression of IGF-I-induced p-IGF-IR/IGF-IR and p-AKT/AKT, but not p-ERK/ERK. In conclusion, the inhibition of cell viability by fucoidan in HT-29 cells may be due to the downregulation of IGF-IR signaling through the main IRS-1/PI3K/AKT pathway. Fucoidan also partially impacted Ras/Raf signaling in the Ras/Raf/ERK pathway. Therefore, we suggest that fucoidan may be a suitable candidate chemopreventive agent in HT-29 colon cancer cells.

https://doi.org/10.18632/oncotarget.10016 Farzaneh Atashrazm, Ray M. Lowenthal, Joanne L. Dickinson, Adele F. Holloway, Gregory M. Woods

Fucoidans have been reported to exert anticancer effects with simultaneous low toxicity against healthy tissue. That correlation was observed in several cancer models, however, it has never been investigated in head and neck cancer before. To magnify the efficacy of conventional therapy, the adminis …

The inflammatory hypothesis is one of the most important mechanisms of depression. Fucoidan is a bioactive sulfated polysaccharide abundant in brown s…

Background Fucoidan extract (FE), an enzymatically digested compound with a low molecular weight, is extracted from brown seaweed. As a natural compound with various actions, FE is attractive, especially in Asian countries, for improving the therapeutic efficacy and safety of cancer treatment. The present study was carried out to investigate the anti-tumor properties of FE in human carcinoma cells and further examine the underlying mechanisms of its activities. Methodology/Principal Finding FE inhibits the growth of MCF-7, MDA-MB-231, HeLa, and HT1080 cells. FE-mediated apoptosis in MCF-7 cancer cells is accompanied by DNA fragmentation, nuclear condensation, and phosphatidylserine exposure. FE induces mitochondrial membrane permeabilization (MMP) through loss of mitochondrial membrane potential (ΔΨm) and regulation of the expression of Bcl-2 family members. Release of apoptosis-inducing factor (AIF) and cytochrome c precedes MMP. AIF release causes DNA fragmentation, the final stage of apoptosis, via a caspase-independent mitochondrial pathway. Additionally, FE was found to induce phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular signal-regulated kinase (ERK) 1/2, and apoptosis was found to be attenuated by inhibition of JNK. Furthermore, FE-mediated apoptosis was found to involve the generation of reactive oxygen species (ROS), which are responsible for the decrease of ΔΨm and phosphorylation of JNK, p38, and ERK1/2 kinases. Conclusions/Significance These data suggest that FE activates a caspase-independent apoptotic pathway in MCF-7 cancer cells through activation of ROS-mediated MAP kinases and regulation of the Bcl-2 family protein-mediated mitochondrial pathway. They also provide evidence that FE deserves further investigation as a natural anticancer and cancer preventive agent.

Fucoidan, the complex fucose-containing sulphated polysaccharide varies considerably in structure, composition, and bioactivity, depending on the source, species, seasonality, and extraction method. In this study, we examined five fucoidans extracted from the same seaweed species Undaria pinnatifida but from different geological locations, and compared them to the laboratory-grade fucoidan from Sigma (S). The five products differed in molecular composition. The amount of over 2 kDa low molecular weight fraction (LMWF) of the New Zealand crude fucoidan (S1) was larger than that of S, and this fraction was unique, compared to the other four fucoidans. The difference of molecular compositions between S and S1 explained our previous observation that S1 exhibited different anticancer profile in some cancer cell lines, compared with S. Since we observed this unique LMWF, we compared the cytotoxic effects of a LMWF and a high molecular weight fucoidan (HMWF) in two breast cancer cell lines—MCF-7 and MDA-MB-231. Results indicated that the molecular weight is a critical factor in determining the anti-cancer potential of fucoidan, from the New Zealand U. pinnatifida, as the LMWF exhibited a dose-dependent inhibition on the proliferation of breast cancer cells, significantly better than the HMWF, in both cell lines. A time-dependent inhibition was only observed in the MCF-7. Induction of caspase-dependent apoptosis was observed in the MDA-MB-231 cells, through the intrinsic apoptosis pathway alone, or with the extrinsic pathway. LMWF stimulated a dose-dependent NOS activation in the MDA-MB-231 cells. In conclusion, the fucoidan extracted from the New Zealand U. pinnatifida contains a unique LMWF, which could effectively inhibit the growth of breast cancer cell lines. Therefore, the LMWF from New Zealand U. pinnatifida could be used as a supplement cancer treatment.

Inflammation induces pancreatic islet cell apoptosis. Effects of fucoidan from Acaudina molpadioides (Am-FUC) on inhibition of pancreatic islet cell apoptosis and inflammation in type 2 diabetic mice were investigated. Am-FUC repaired pancreatic islet cells, decreased serum C-reactive protein (CRP), macrophage inflammatory protein 1 (MIP-1), interleukin 1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) levels, and increased the IL-10 level. Am-FUC also reduced TNF-α, CRP, MIP-1, IL-1β, and IL-6 mRNA expressions, and increased IL-10 mRNA expression in epididymal adipose tissues. Am-FUC reduced Bid, Bax, cytochrome c, caspase 9, and caspase 3 mRNA expressions, and increased Bcl-2 and Bcl-xL mRNA expressions. Am-FUC down-regulated t-Bid, Bax, cytochrome c, and caspase 9 activities, cleaved caspase 3 proteins, and up-regulated Bcl-2 and Bcl-xL proteins. Thus, an Am-FUCblocked mitochondrial pathway was the suppression mechanism in pancreatic islet cell apoptosis via regulation of inflammatory cytokines providing dietary intervention in type 2 diabetes and inflammation-induced pancreatic islet apoptosis.

Antibiotic treatment, as an important therapeutic intervention, can cause damage to the host microbiome and the intestinal mucosal barrier. In order to find a way to alleviate the side effects of antibiotics, the present study investigated the effects of fucoidan (ANP) isolated from Ascophyllum nodosum on gu

Ecklonia maxima, an endemic South African seaweed, is a potential source of beneficial bioactive compounds. Among these compounds, fucoidan, a sulphat…

Fucoidan is a marine-origin sulfated polysaccharide that can show anticancer activity, to which both pro- and anti-angiogenic responses have been repo…

Background Hepatitis B virus (HBV) infection is a serious public health problem leading to cirrhosis and hepatocellular carcinoma. As the clinical utility of current therapies is limited, the development of new therapeutic approaches for the prevention and treatment of HBV infection is imperative. Fucoidan is a natural sulfated polysaccharide that extracted from different species of brown seaweed, which was reported to exhibit various bioactivities. However, it remains unclear whether fucoidan influences HBV replication or not. Methods The HBV-infected mouse model was established by hydrodynamic injection of HBV replicative plasmid, and the mice were treated with saline or fucoidan respectively. Besides, we also tested the inhibitory effect of fucoidan against HBV infection in HBV-transfected cell lines. Results The result showed that fucoidan from Fucus vesiculosus decreased serum HBV DNA, HBsAg and HBeAg levels and hepatic HBcAg expression in HBV-infected mice. Moreover, fucoidan treatment also suppressed intracellular HBcAg expression and the secretion of the HBV DNA as well as HBsAg and HBeAg in HBV-expressing cells. Furthermore, we proved that the inhibitory activity by fucoidan was due to the activation of the extracellular signal-regulated kinase (ERK) pathway and the subsequent production of type I interferon. Using specific inhibitor of ERK pathway abrogated the fucoidan-mediated inhibition of HBV replication. Conclusion This study highlights that fucoidan might be served as an alternative therapeutic approach for the treatment of HBV infection.

Fucoidan from sea cucumber is reported to exhibit anti-hyperglycaemic effect, but its influence on pancreatic islets is lacking. The effects of fucoid …

Fucoidan is a fucose-rich polysaccharide that has gained attention for its various anticancer properties. However, the effect and underlying mechanism…

Poor pancreatic cancer (PC) prognosis has been attributed to its resistance to apoptosis and propensity for early systemic dissemination. Existing the…

Cardiovascular diseases, including heart attacks and strokes, continue to be the leading causes of deaths resulting in more than 17 million deaths each year worldwide. Cardiovascular disease (CVD) man...

Fucoidan, a sulfated polysaccharide derived from brown seaweeds, has been shown to reduce blood glucose levels and improve insulin sensitivity in mice…

Despite major scientific advances in its prevention, treatment and care, hypertension remains a serious condition that might lead to long-term complications such as heart disease and stroke. The great majority of forms of hypertension eventually result from an increased vasomotor tone activity that is regula

Fucoidan is a sulfated polysaccharide widely distributed in brown seaweed. It exhibits several bioactivities, such as anti-cancer, anti-tumor, anti-microbial, anti-diabetic and anti-oxidant properties. However, the effects of fucoidan in chondrocytes are not well established. Previously, we have reported in vitro and in vivo anti-inflammatory effects of fucoidan. In this study, we evaluated the effects and regulatory mechanism of fucoidan derived from Undaria pinnatifida on the cyclooxygenase-2 (COX-2) and type II collagen in rabbit articular chondrocytes. Using western blotting and alcian blue staining, respectively, fucoidan was shown to induce type II collagen and sulfated proteoglycan in a dose- and time-dependent manner. Moreover, fucoidan inhibited the COX-2 expression in a dose- and time-dependent manner and increased the phosphorylation of extracellular signal-regulated kinase (ERK), p38, and AKT kinases in chondrocytes. The inhibition of p38 and AKT using SB203580 and LY294002, respectively, in the presence of fucoidan decreased the expression of type II collagen. However, ERK inhibition using PD98050 stimulated type II collagen expression. Fucoidan increased COX-2 expression in the presence of inhibitors of ERK, p38, and AKT kinases. These results conclusively suggested that fucoidan regulated type II collagen expression via the p38 and AKT pathways, and COX-2 expression via the p38, ERK and AKT pathways in rabbit articular chondrocytes. Moreover, given its ability to mediate cell differentiation and exert anti-inflammatory activity, fucoidan may represent a potential therapeutic substance for use in inflammatory conditions, including arthritis.

The use of fucoidan, a marine-origin bioactive polymer, is herein proposed as a component of an innovative and effective strategy against melanoma, one of the most aggressive skin cancers. First, fucoidan antitumor activity, in its soluble form, was assessed presenting increased cytotoxicity over melanoma cells when compared to human dermal fibroblasts and keratinocytes. After this antitumor activity validation and trying to develop a more targeted and local strategy aiming to diminish the cytotoxic effects over noncancer cells, fucoidan was immobilized at the surface of an electrospun nanofiber mesh (NFM_Fu), envisioning the development of a therapeutic patch. The maximum immobilization concentration was 1.2 mg mL–1, determined by the Toluidine Blue Assay and confirmed by XPS. Furthermore, NFM_Fu is more hydrophilic than NFM, presenting a contact angle of 36°, lower than the 121° of the control condition. NFM_Fu was able to reduce human melanoma cell viability by 50% without affecting human dermal fibroblasts and keratinocytes. Taken together, these results set the basis for a valuable approach for melanoma treatment.

Chronic kidney disease (CKD) is a significant risk factor for cardiovascular and peripheral vascular disease. Although mesenchymal stem cell (MSC)-bas…

Hyperlipidemia is associated with increased risk of the development of cardiovascular diseases. Although a great deal of attention has been paid to th…

Gefitinib is a first tyrosine kinase inhibitor (TKI) designed with an EGFR tyrosine kinase for lung cancer targeted therapy. However, some lung cancer…

Background Cancer metastasis is the main cause leading to disease recurrence and high mortality in cancer patients. Therefore, inhibiting metastasis process or killing metastatic cancer cells by inducing apoptosis is of clinical importance in improving cancer patient survival. Previous studies revealed that fucoidan, a fucose-rich polysaccharide isolated from marine brown alga, is a promising natural product with significant anti-cancer activity. However, little is known about the role of endoplasmic reticulum (ER) stress in fucoidan-induced cell apoptosis. Principal Findings We reported that fucoidan treatment inhibits cell growth and induces apoptosis in cancer cells. Fucoidan treatments resulted in down-regulation of the glucose regulated protein 78 (GRP78) in the metastatic MDA-MB-231 breast cancer cells, and of the ER protein 29 (ERp29) in the metastatic HCT116 colon cancer cells. However, fucoidan treatment promoted ER Ca2+-dependent calmodulin-dependent kinase II (CaMKII) phosphorylation, Bcl-associated X protein (Bax) and caspase 12 expression in MDA-MB-231 cells, but not in HCT116 cells. In both types of cancer cells, fucoidan activated the phosphorylation of eukaryotic initiation factor 2 alpha (p-eIF2α)\CCAAT/enhancer binding protein homologous protein (CHOP) pro-apoptotic cascade and inhibited the phosphorylation of inositol-requiring kinase 1 (p-IRE-1)\X-box binding proteins 1 splicing (XBP-1s) pro-survival cascade. Furthermore, CHOP knockdown prevented DNA damage and cell death induced by fucoidan. Conclusion/Significance Fucoidan exerts its anti-tumor function by modulating ER stress cascades. Contribution of ER stress to the fucoidan-induced cell apoptosis augments our understanding of the molecular mechanisms underlying its anti-tumour activity and provides evidence for the therapeutic application of fucoidan in cancer.

(2016). Fucoidan Induces Cell Aggregation and Apoptosis in Osteosarcoma MG-63 Cells. Animal Cells and Systems: Vol. 20, No. 4, pp. 186-192.

Preclinical Research Fucoidan, a sulfated polysaccharide, is a compound found in various species of seaweed that has anti-viral, anti-bacterial, anti-oxidant, anti-inflammatory, and immuno...