Fucoidan Abstracts 1

© 2012

Heterofucans from the brown seaweed Canistrocarpus cervicornis with anticoagulant and antioxidant activities

            (Camara, Costa et al. 2011) Download

Fucan is a term used to denominate a family of sulfated polysaccharides rich in sulfated l-fucose. We extracted six fucans from Canistrocarpus cervicornis by proteolytic digestion followed by sequential acetone precipitation. These heterofucans are composed mainly of fucose, glucuronic acid, galactose and sulfate. No polysaccharide was capable of prolonging prothrombin time (PT) at the concentration assayed. However, all polysaccharides prolonged activated partial thromboplastin time (aPTT). Four sulfated polysaccharides (CC-0.3/CC-0.5/CC-0.7/CC-1.0) doubled aPTT with only 0.1 mg/mL of plasma, only 1.25-fold less than Clexane, a commercial low molecular weight heparin. Heterofucans exhibited total antioxidant capacity, low hydroxyl radical scavenging activity, good superoxide radical scavenging efficiency (except CC-1.0), and excellent ferrous chelating ability (except CC-0.3). These results clearly indicate the beneficial effect of C. cervicornis polysaccharides as anticoagulants and antioxidants. Further purification steps and additional studies on structural features as well as in vivo experiments are needed to test the viability of their use as therapeutic agents.

A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds

            (Cumashi, Ushakova et al. 2007) Download

The anti-inflammatory, antiangiogenic, anticoagulant, and antiadhesive properties of fucoidans obtained from nine species of brown algae were studied in order to examine the influence of fucoidan origin and composition on their biological activities. All fucoidans inhibited leucocyte recruitment in an inflammation model in rats, and neither the content of fucose and sulfate nor other structural features of their polysaccharide backbones significantly affected the efficacy of fucoidans in this model. In vitro evaluation of P-selectin-mediated neutrophil adhesion to platelets under flow conditions revealed that only polysaccharides from Laminaria saccharina, L. digitata, Fucus evanescens, F. serratus, F. distichus, F. spiralis, and Ascophyllum nodosum could serve as P-selectin inhibitors. All fucoidans, except that from Cladosiphon okamuranus carrying substantial levels of 2-O-alpha-D-glucuronopyranosyl branches in the linear (1-->3)-linked poly-alpha-fucopyranoside chain, exhibited anticoagulant activity as measured by activated partial thromboplastin time whereas only fucoidans from L. saccharina, L. digitata, F. serratus, F. distichus, and F. evanescens displayed strong antithrombin activity in a platelet aggregation test. The last fucoidans potently inhibited human umbilical vein endothelial cell (HUVEC) tubulogenesis in vitro and this property correlated with decreased levels of plasminogen-activator inhibitor-1 in HUVEC supernatants, suggesting a possible mechanism of fucoidan-induced inhibition of tubulogenesis. Finally, fucoidans from L. saccharina, L. digitata, F. serratus, F. distichus, and F. vesiculosus strongly blocked MDA-MB-231 breast carcinoma cell adhesion to platelets, an effect which might have critical implications in tumor metastasis. The data presented herein provide a new rationale for the development of potential drugs for thrombosis, inflammation, and tumor progression.

Evaluation of marine brown algae and sponges from Brazil as anticoagulant and antiplatelet products

            (de Andrade Moura, Ortiz-Ramirez et al. 2011) Download

The ischemic disorders, in which platelet aggregation and blood coagulation are involved, represent a major cause of disability and death worldwide. The antithrombotic therapy has unsatisfactory performance and may produce side effects. So, there is a need to seek molecules with antithrombotic properties. Marine organisms produce substances with different well defined ecological functions. Moreover, some of these molecules also exhibit pharmacological properties such as antiviral, anticancer, antiophidic and anticoagulant properties. The aim of this study was to evaluate, through in vitro tests, the effect of two extracts of brown algae and ten marine sponges from Brazil on platelet aggregation and blood coagulation. Our results revealed that most of the extracts were capable of inhibiting platelet aggregation and clotting measured by plasma recalcification tests, prothrombin time, activated partial thromboplastin time, and fibrinogenolytic activity. On the other hand, five of ten species of sponges induced platelet aggregation. Thus, the marine organisms studied here may have molecules with antithrombotic properties, presenting biotechnological potential to antithrombotic therapy. Further chemical investigation should be conducted on the active species to discover useful molecules for the development of new drugs to treat clotting disorders.

Prophylactic effect of dietary seaweed Fucoidan against enteral prion infection

            (Doh-Ura, Kuge et al. 2007) Download

Dietary seaweed fucoidan delays the onset of disease of enterally infected mice with scrapie when given orally for 6 days after infection, but not when given before the infection. This effect was not modified at a tested fucoidan dose range and appeared to reach the maximum level at a concentration of 2.5% or less in feed. Daily uptake of fucoidan might be prophylactic against prion diseases caused by ingestion of prion-contaminated materials, although further evaluation of its pharmacology remains to be done.

Therapies from fucoidan multifunctional marine polymers

         (Fitton 2011) Download

Published research on fucoidans increased three fold between 2000 and 2010. These algal derived marine carbohydrate polymers present numerous valuable bioactivities. This review discusses the role for fucoidan in the control of acute and chronic inflammation via selectin blockade, enzyme inhibition and inhibiting the complement cascade. The recent data on toxicology and uptake of fucoidan is detailed together with a discussion on the comparative activities of fractions of fucoidan from different sources. Recent in vivo, in vitro and clinical research related to diverse clinical needs is discussed. Targets include osteoarthritis, kidney and liver disease, neglected infectious diseases, hemopoietic stem cell modulation, protection from radiation damage and treatments for snake envenomation. In recent years, the production of well characterized reproducible fucoidan fractions on a commercial scale has become possible making therapies from fucoidan a realizable goal.

A natural seaweed derived mineral supplement (Aquamin F) for knee osteoarthritis: a randomised, placebo controlled pilot study

            (Frestedt, Kuskowski et al. 2009) Download

BACKGROUND: Osteoarthritis (OA) is a slowly destructive process that may be influenced by a nutritional mineral balance in the body. METHODS: This small, double blind, placebo controlled pilot study investigated the impact of treatment with a natural multi-mineral supplement from seaweed (Aquamin) on 6 minute walking distance (6 MWD), range of motion (ROM), and pain and joint mobility measured by the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index in subjects with moderate to severe OA of the knee during gradual withdrawal of non-steroidal anti-inflammatory drugs (NSAIDs) that were being used daily for pain management. Subjects (n = 29) with moderate to severe OA of the knee were randomised to receive either Aquamin (2400 mg/d) or Placebo for up to 12 weeks. RESULTS: Of the 29 subjects initially randomized, only 22 subjects proceeded to treatment due to 7 subjects not meeting study selection criteria at baseline. Fourteen subjects completed the study and an ITT analysis (n = 22) of the data showed no significant differences in WOMAC scores however, the data did reveal significant improvements in passive and active extension ROM (0.83 degrees +/- 1.54 vs. -1.54 degrees +/- 2.43; difference, 5.2 degrees +/- 2.2, p = 0.028) and 6 MWD (150 +/- 48 ft vs. 12.5 +/- 31.5 ft; difference, 136 +/- 57 ft, p = 0.03) in the Aquamin group compared to the placebo group; respectively, following a 50% reduction in NSAID use. The treatments were well tolerated and the adverse event profiles were not significantly different between the groups. CONCLUSION: This small preliminary study suggests Aquamin may increase range of motion and walking distances in subjects with OA of the knee and may allow partial withdrawal of NSAIDs over 12 weeks of treatment. Additional research is needed to confirm these preliminary observations. TRIAL REGISTRATION: NCT00755482.

Chemical structures and bioactivities of sulfated polysaccharides from marine algae        

         (Jiao, Yu et al. 2011) Download

Sulfated polysaccharides and their lower molecular weight oligosaccharide derivatives from marine macroalgae have been shown to possess a variety of biological activities. The present paper will review the recent progress in research on the structural chemistry and the bioactivities of these marine algal biomaterials. In particular, it will provide an update on the structural chemistry of the major sulfated polysaccharides synthesized by seaweeds including the galactans (e.g., agarans and carrageenans), ulvans, and fucans. It will then review the recent findings on the anticoagulant/antithrombotic, antiviral, immuno-inflammatory, antilipidemic and antioxidant activities of sulfated polysaccharides and their potential for therapeutic application.

Biological effects of fucoidan isolated from Fucus vesiculosus on thrombosis and vascular cells

            (Kwak, Cho et al. 2010) Download

BACKGROUND: Fucoidan is a highly sulfated glycosaminoglycan, which has a molecular structure similar to that of heparin. The antithrombotic effects of fucoidan in vitro have been widely reported, but its antithrombotic effects in vivo as well as its other biological properties in vitro have not been well investigated. METHODS: This study investigated the effects and mechanism of fucoidan from Fucus vesiculosus on thrombosis both in vitro and in vivo. A ferric chloride-induced mouse carotid artery thrombosis model was used to determine the antithrombotic effects of fucoidan in vivo. Additionally, changes in the levels of proinflammatory cytokines and chemokines were examined in vascular cells treated with fucoidan. RESULTS: In vivo studies employing a ferric chloride-induced mouse carotid artery thrombosis model indicated that fucoidan had a stronger antithrombotic activity than heparin. Further, vascular cells treated with fucoidan demonstrated a decrease in proinflammatory cytokine and chemokine production as well as inhibition of proliferation. CONCLUSION: The major findings of this study showed that fucoidan has a stronger antithrombotic effect than heparin in vivo and that fucoidan has an inhibitory effect on proinflammatory cytokine production and proliferation of vascular cells.

Marine bioactives as functional food ingredients: potential to reduce the incidence of chronic diseases

            (Lordan, Ross et al. 2011) Download

The marine environment represents a relatively untapped source of functional ingredients that can be applied to various aspects of food processing, storage, and fortification. Moreover, numerous marine-based compounds have been identified as having diverse biological activities, with some reported to interfere with the pathogenesis of diseases. Bioactive peptides isolated from fish protein hydrolysates as well as algal fucans, galactans and alginates have been shown to possess anticoagulant, anticancer and hypocholesterolemic activities. Additionally, fish oils and marine bacteria are excellent sources of omega-3 fatty acids, while crustaceans and seaweeds contain powerful antioxidants such as carotenoids and phenolic compounds. On the basis of their bioactive properties, this review focuses on the potential use of marine-derived compounds as functional food ingredients for health maintenance and the prevention of chronic diseases.

Anticoagulant, Antioxidant and Antitumor Activities of Heterofucans from the Seaweed Dictyopteris delicatula

(Magalhaes, Costa et al. 2011) Download

In the present study, six families of sulfated polysaccharides were obtained from seaweed Dictyopteris delicatula by proteolytic digestion, followed by acetone fractionation and molecular sieving on Sephadex G-100. Chemical analyses demonstrated that all polysaccharides contain heterofucans composed mainly of fucose, xylose, glucose, galactose, uronic acid, and sulfate. The fucans F0.5v and F0.7v at 1.0 mg/mL showed high ferric chelating activity ( approximately 45%), whereas fucans F1.3v (0.5 mg/mL) showed considerable reducing power, about 53.2% of the activity of vitamin C. The fucan F1.5v presented the most prominent anticoagulant activity. The best antiproliferative activity was found with fucans F1.3v and F0.7v. However, F1.3v activity was much higher than F0.7v inhibiting almost 100% of HeLa cell proliferation. These fucans have been selected for further studies on structural characterization as well as in vivo experiments, which are already in progress.

Fucoidan promotes mechanosensory hair cell regeneration following amino glycoside-induced cell death

            (Moon, So et al. 2011) Download

OBJECTIVE: Lateral line system of the zebrafish is a useful model for study of hair cell toxicity and regeneration. We found that low molecular weight fucoidan (LMWF) stimulated the regeneration of mechanosensory hair cells after neomycin-induced cell death in zebrafish lateral line. The aims of this study were to quantify the regenerative effects of LMWF and determine their relationship to the Notch and FGF signaling pathways. METHODS: Wild-type zebrafish and three different transgenic zebrafish lines (Pou4f3::GFP, scm1::GFP, and ET20::GFP) were used. At 4.5-6 days post-fertilization, lateral line hair cells of larvae were eliminated using neomycin (500 muM). Larvae were then treated with LMWF. Neuromasts were observed using confocal microscopy. Stereocilia morphology was observed using scanning electron microscopy, and the location and status of regeneration was assessed using 5-bromo-2-deoxyuridine (BrdU) incorporation. RESULTS: Hair cells damaged by neomycin treatment regenerated faster in wild-type and Pou4f3::GFP larvae treated with LMWF (50 mug/ml) than in untreated controls. LMWF also enhanced the regeneration of supporting cells in scm1::GFP and ET20::GFP larvae. Increased numbers of BrdU-labeled cells were found after LMWF treatment in neuromast regions corresponding to internal and peripheral supporting cells. The effect of LMWF was mimicked by the Notch signaling inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT), but the effects of LMWF and DAPT were not additive. CONCLUSION: LMWF enhances the regeneration of hair cells damaged by neomycin. The mechanism may involve the Notch signaling pathway. LMWF shows promise as a therapeutic agent for hearing and balance disorders.

A combined phase I and II open label study on the effects of a seaweed extract nutrient complex on osteoarthritis

            (Myers, O'Connor et al. 2010) Download

BACKGROUND: Isolated fucoidans from brown marine algae have been shown to have a range of anti-inflammatory effects. PURPOSE: This present study tested a Maritech((R)) extract formulation, containing a blend of extracts from three different species of brown algae, plus nutrients in an open label combined phase I and II pilot scale study to determine both acute safety and efficacy in osteoarthritis of the knee. PATIENTS AND METHODS: Participants (n = 12, five females [mean age, 62 +/- 11.06 years] and seven males [mean age, 57.14 +/- 9.20 years]) with a confirmed diagnosis of osteoarthritis of the knee were randomized to either 100 mg (n = 5) or 1000 mg (n = 7) of a Maritech((R)) extract formulation per day. The formulation contained Maritech((R)) seaweed extract containing Fucus vesiculosis (85% w/w), Macrocystis pyrifera (10% w/w) and Laminaria japonica (5% w/w) plus vitamin B6, zinc and manganese. Primary outcome was the average comprehensive arthritis test (COAT) score which is comprised of four sub-scales: pain, stiffness, difficulty with physical activity and overall symptom severity measured weekly. Safety measures included full blood count, serum lipids, liver function tests, urea, creatinine and electrolytes determined at baseline and week 12. All adverse events were recorded. RESULTS: Eleven participants completed 12 weeks and one completed 10 weeks of the study. Using a multilevel linear model, the average COAT score was reduced by 18% for the 100 mg treatment and 52% for the 1000 mg dose at the end of the study. There was a clear dose response effect seen between the two treatments (P </= 0.0005) on the average COAT score and each of the four COAT subscales (pain, stiffness, difficulty with physical activity and overall symptom severity) (P </= 0.05). The preparation was well tolerated and the few adverse events were unlikely to be related to the study medication. There were no changes in blood parameters measured over the course of the study with the exception of an increase in serum albumin which was not clinically significant. CONCLUSION: The seaweed extract nutrient complex when taken orally over twelve weeks decreased the symptoms of osteoarthritis in a dose-dependent manner. It was demonstrated to be safe to use over the study period at the doses tested. The efficacy of the preparation now needs to be demonstrated in a phase III randomized controlled trial (RCT). AUSTRALIAN AND NEW ZEALAND CLINICAL TRIALS REGISTER: ACTRN12607000229471.

Structure, biology, evolution, and medical importance of sulfated fucans and galactans

         (Pomin and Mourao 2008) Download

Sulfated fucans and galactans are strongly anionic polysaccharides found in marine organisms. Their structures vary among species, but their major features are conserved among phyla. Sulfated fucans are found in marine brown algae and echinoderms, whereas sulfated galactans occur in red and green algae, marine angiosperms, tunicates (ascidians), and sea urchins. Polysaccharides with 3-linked, beta-galactose units are highly conserved in some taxonomic groups of marine organisms and show a strong tendency toward 4-sulfation in algae and marine angiosperms, and 2-sulfation in invertebrates. Marine algae mainly express sulfated polysaccharides with complex, heterogeneous structures, whereas marine invertebrates synthesize sulfated fucans and sulfated galactans with regular repetitive structures. These polysaccharides are structural components of the extracellular matrix. Sulfated fucans and galactans are involved in sea urchin fertilization acting as species-specific inducers of the sperm acrosome reaction. Because of this function the structural evolution of sulfated fucans could be a component in the speciation process. The algal and invertebrate polysaccharides are also potent anticoagulant agents of mammalian blood and represent a potential source of compounds for antithrombotic therapies.

The effect of Fucus vesiculosus, an edible brown seaweed, upon menstrual cycle length and hormonal status in three pre-menopausal women: a case report

            (Skibola 2004) Download

BACKGROUND: Rates of estrogen-dependent cancers are among the highest in Western countries and lower in the East. These variations may be attributable to differences in dietary exposures such as higher seaweed consumption among Asian populations. The edible brown kelp, Fucus vesiculosus (bladderwrack), as well as other brown kelp species, lower plasma cholesterol levels. Since cholesterol is a precursor to sex hormone biosynthesis, kelp consumption may alter circulating sex hormone levels and menstrual cycling patterns. In particular, dietary kelp may be beneficial to women with or at high risk for estrogen-dependent diseases. To test this, bladderwrack was administered to three pre-menopausal women with abnormal menstrual cycling patterns and/or menstrual-related disease histories. CASE PRESENTATION: Intake of bladderwrack was associated with significant increases in menstrual cycle lengths, ranging from an increase of 5.5 to 14 days. In addition, hormone measurements ascertained for one woman revealed significant anti-estrogenic and progestagenic effects following kelp administration. Mean baseline 17beta-estradiol levels were reduced from 626 +/- 91 to 164 +/- 30 pg/ml (P = 0.04) following 700 mg/d, which decreased further to 92.5.0 +/- 3.5pg/ml (P = 0.03) with the 1.4 g/d dose. Mean baseline progesterone levels rose from 0.58 +/- 0.14 to 8.4 +/- 2.6 ng/ml with the 700 mg/d dose (P = 0.1), which increased further to 16.8 +/- 0.7 ng/ml with the 1.4 g/d dose (P = 0.002). CONCLUSIONS: These pilot data suggest that dietary bladderwrack may prolong the length of the menstrual cycle and exert anti-estrogenic effects in pre-menopausal women. Further, these studies also suggest that seaweed may be another important dietary component apart from soy that is responsible for the reduced risk of estrogen-related cancers observed in Japanese populations. However, these studies will need to be performed in well-controlled clinical trials to confirm these preliminary findings.

Could dietary seaweed reverse the metabolic syndrome?

            (Teas, Baldeon et al. 2009) Download

Incidence of the metabolic syndrome is increasing worldwide, with notable exceptions of some Asian countries where seaweeds are commonly consumed. 13 men (mean age 47.4+/-9.9 yr) and 14 women (average age 45.6+/-12.2 yr) with at least one symptom of the metabolic syndrome were recruited in Quito Ecuador to a randomized double-blinded placebo-controlled trial. Subjects were assigned to either Group 1 (1 m placebo, followed by 1 m 4 g/d seaweed [Undaria pinnatifida]) or Group 2 (1 m of 4 g/d seaweed, followed by 1 m of 6 g/d of seaweed). Blood pressure, weight, waist circumference, inflammation biomarkers, and lipids were measured monthly. Repeated measures analysis of variance with Tukey's multiple comparison tests were used for statistical analysis. In Group 2, systolic blood pressure decreased 10.5 mmHg after a month of 6 g/d seaweed (95% CI: 4.1, 16.8 mmHg; p<0.05), primarily in subjects with high-normal baseline blood pressure. Waist circumference changed only for women participants, with a 2.4 cm decrease in Group 1 after treatment with placebo (95% CI: 1.0, 3.7 cm; p<0.01). In Group 2, women had a mean decrease of 2.1 cm after 4 g/d (95% CI: 0.4, 3.7 cm; p<0.05) and a further 1.8 cm decrease after 1 m 6 g/d seaweed (95 % CI: 0.1, 3.4, p<0.05). No other changes were observed. Consumption of 4 to 6 g/d seaweed, typical for most people in Japan, may be associated with low metabolic syndrome prevalence.

Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women

            (Teas, Hurley et al. 2009) Download

Seaweed and soy foods are consumed daily in Japan, where breast cancer rates for postmenopausal women are significantly lower than in the West. Likely mechanisms include differences in diet, especially soy consumption, and estrogen metabolism. Fifteen healthy postmenopausal women participated in this double-blind trial of seaweed supplementation with soy challenge. Participants were randomized to 7 wk of either 5 g/d seaweed (Alaria) or placebo (maltodextrin). During wk 7, participants also consumed a daily soy protein isolate (2 mg isoflavones/kg body weight). After a 3-wk washout period, participants were crossed over to the alternate supplement schedule. There was an inverse correlation between seaweed dose (mg/kg body weight) and serum estradiol (E2) (seaweed-placebo = y = -2.29 x dose + 172.3; r = -0.70; P = 0.003), [corrected] which was linear across the range of weights. Soy supplementation increased urinary daidzein, glycitein, genistein, and O-desmethylangolensin (P = 0.0001) and decreased matairesinol and enterolactone (P < 0.05). Soy and seaweed plus soy (SeaSoy) increased urinary excretion of 2-hydroxyestrogen (2-OHE) (P = 0.0001) and the ratio of 2-OHE:16alpha-hydroxyestrone (16alphaOHE(1)) (P = 0.01). For the 5 equol excretors, soy increased urinary equol excretion (P = 0.0001); the combination of SeaSoy further increased equol excretion by 58% (P = 0.0001). Equol producers also had a 315% increase in 2:16 ratio (P = 0.001) with SeaSoy. Seaweed favorably alters estrogen and phytoestrogen metabolism and these changes likely include modulation of colonic bacteria.

Biological properties of sulfated fucans: the potent inhibiting activity of algal fucoidan against the human compliment system

            (Tissot and Daniel 2003) Download

A case-control study on seaweed consumption and the risk of breast cancer

            (Yang, Nam et al. 2010) Download

Gim (Porphyra sp.) and miyeok (Undaria pinnatifida) are the seaweeds most consumed by Koreans. We investigated the association between the intake of gim and miyeok and the risk of breast cancer in a case-control study. Cases were 362 women aged 30-65 years old, who were histologically confirmed to have breast cancer. Controls visiting the same hospital were matched to cases according to their age (sd 2 years) and menopausal status. Food intake was estimated by the quantitative FFQ with 121 items, including gim and miyeok. Conditional logistic regression analysis was used to obtain the OR and corresponding 95 % CI. The average intake and consumption frequency of gim in cases were lower than in controls. The daily intake of gim was inversely associated with the risk of breast cancer (5th v. 1st quintile, OR, 0.48; 95 % CI, 0.27, 0.86; P for trend, 0.026) after adjustment for potential confounders. After stratification analysis was performed according to menopausal status, premenopausal women (5th v. 1st quintile, OR, 0.44; 95 % CI, 0.24, 0.80; P for trend, 0.007) and postmenopausal women (5th v. 1st quintile, OR, 0.32; 95 % CI, 0.13, 0.80; P for trend, 0.06) showed similar inverse associations between gim intake and the risk of breast cancer after an adjustment for potential confounders except dietary factors. Miyeok consumption did not have any significant associations with breast cancer. These results suggest that high intake of gim may decrease the risk of breast cancer.

Fucoidan extract induces apoptosis in MCF-7 cells via a mechanism involving the ROS-dependent JNK activation and mitochondria-mediated pathways

            (Zhang, Teruya et al. 2011) Download

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 (DeltaPsim) 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 DeltaPsim 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.


Camara, R. B., L. S. Costa, et al. (2011). "Heterofucans from the brown seaweed Canistrocarpus cervicornis with anticoagulant and antioxidant activities." Mar Drugs 9(1): 124-38.

Cumashi, A., N. A. Ushakova, et al. (2007). "A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds." Glycobiology 17(5): 541-52.

de Andrade Moura, L., F. Ortiz-Ramirez, et al. (2011). "Evaluation of marine brown algae and sponges from Brazil as anticoagulant and antiplatelet products." Mar Drugs 9(8): 1346-58.

Doh-Ura, K., T. Kuge, et al. (2007). "Prophylactic effect of dietary seaweed Fucoidan against enteral prion infection." Antimicrob Agents Chemother 51(6): 2274-7.

Fitton, J. H. (2011). "Therapies from fucoidan; multifunctional marine polymers." Mar Drugs 9(10): 1731-60.

Frestedt, J. L., M. A. Kuskowski, et al. (2009). "A natural seaweed derived mineral supplement (Aquamin F) for knee osteoarthritis: a randomised, placebo controlled pilot study." Nutr J 8: 7.

Jiao, G., G. Yu, et al. (2011). "Chemical structures and bioactivities of sulfated polysaccharides from marine algae." Mar Drugs 9(2): 196-223.

Kwak, K. W., K. S. Cho, et al. (2010). "Biological effects of fucoidan isolated from Fucus vesiculosus on thrombosis and vascular cells." Korean J Hematol 45(1): 51-7.

Lordan, S., R. P. Ross, et al. (2011). "Marine bioactives as functional food ingredients: potential to reduce the incidence of chronic diseases." Mar Drugs 9(6): 1056-100.

Magalhaes, K. D., L. S. Costa, et al. (2011). "Anticoagulant, Antioxidant and Antitumor Activities of Heterofucans from the Seaweed Dictyopteris delicatula." Int J Mol Sci 12(5): 3352-3365.

Moon, I. S., J. H. So, et al. (2011). "Fucoidan promotes mechanosensory hair cell regeneration following amino glycoside-induced cell death." Hear Res 282(1-2): 236-42.

Myers, S. P., J. O'Connor, et al. (2010). "A combined phase I and II open label study on the effects of a seaweed extract nutrient complex on osteoarthritis." Biologics 4: 33-44.

Pomin, V. H. and P. A. Mourao (2008). "Structure, biology, evolution, and medical importance of sulfated fucans and galactans." Glycobiology 18(12): 1016-27.

Skibola, C. F. (2004). "The effect of Fucus vesiculosus, an edible brown seaweed, upon menstrual cycle length and hormonal status in three pre-menopausal women: a case report." BMC Complement Altern Med 4: 10.

Teas, J., M. E. Baldeon, et al. (2009). "Could dietary seaweed reverse the metabolic syndrome?" Asia Pac J Clin Nutr 18(2): 145-54.

Teas, J., T. G. Hurley, et al. (2009). "Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women." J Nutr 139(5): 939-44.

Tissot, B. and R. Daniel (2003). "Biological properties of sulfated fucans: the potent inhibiting activity of algal fucoidan against the human compliment system." Glycobiology 13(12): 29G-30G.

Yang, Y. J., S. J. Nam, et al. (2010). "A case-control study on seaweed consumption and the risk of breast cancer." Br J Nutr 103(9): 1345-53.

Zhang, Z., K. Teruya, et al. (2011). "Fucoidan extract induces apoptosis in MCF-7 cells via a mechanism involving the ROS-dependent JNK activation and mitochondria-mediated pathways." PLoS One 6(11): e27441.