Unveiling the Potential of Ultrasonic-Assisted Ethanol Extract from Sargassum horneri in Inhibiting Tyrosinase Activity and Melanin Production in B16F10 Murine Melanocytes.

BACKGROUNDS: Melanogenesis, regulated by genetic, hormonal, and environmental factors, occurs in melanocytes in the basal layer of the epidermis. Dysregulation of this process can lead to various skin disorders, such as hyperpigmentation and hypopigmentation. Therefore, the present study investigated the effect of ultrasonic-assisted ethanol extract (SHUE) from Sargassum horneri (S. horneri), brown seaweed against melanogenesis in α-melanocyte-stimulating hormone (MSH)-stimulated B16F10 murine melanocytes. METHODS: Firstly, yield and proximate compositional analysis of the samples were conducted. The effect of SHUE on cell viability has been evaluated by using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. After that, the melanin content and cellular tyrosinase activity in α-MSH-stimulated B16F10 murine melanocytes were examined. Western blot analysis was carried out to investigate the protein expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and tyrosinase-related protein-2 (TRP2). In addition, the effect of extracellular signal-regulated kinase (ERK) on the melanogenesis process was assessed via Western blotting. RESULTS: As per the analysis, SHUE contained the highest average yield on a dry basis at 28.70 ± 3.21%. The findings showed that SHUE reduced the melanin content and cellular tyrosinase activity in α-MSH-stimulated B16F10 murine melanocytes. Additionally, the expression levels of MITF, TRP1, and TRP2 protein were significantly downregulated by SHUE treatment in α-MSH-stimulated B16F10 murine melanocytes. Moreover, SHUE upregulated the phosphorylation of ERK and AKT in α-MSH-stimulated B16F10 murine melanocytes. In addition, experiments conducted using the ERK inhibitor (PD98059) revealed that the activity of SHUE depends on the ERK signaling cascade. CONCLUSION: These results suggest that SHUE has an anti-melanogenic effect and can be used as a material in the formulation of cosmetics related to whitening and lightening.

Anti-Melanogenesis and Anti-Photoaging Effects of the Sulfated Polysaccharides Isolated from the Brown Seaweed Padina boryana.

Sulfated polysaccharides isolated from seaweeds are thought of as ideal ingredients in the pharmaceutical, nutraceutical, and cosmetics industries. Our previous study isolated and characterized sulfated polysaccharides from Padina boryana. The sulfated polysaccharides of Padina boryana (PBP) were extracted, and the antioxidant activity of PBP was evaluated. The results indicate that PBP possesses antioxidant effects and potential in the cosmetic industry. To further investigate the potential of PBP in cosmetics, the photoprotective and anti-melanogenesis effects of PBP were evaluated. The anti-melanogenesis test results display that PBP reduced the melanin content in the murine melanoma cells stimulated by alpha melanocyte-stimulating hormone from 203.7% to 183.64%, 144.63%, and 127.57% at concentrations of 25 µg/mL, 50 µg/mL, and 100 µg/mL, respectively. The anti-photodamage test results showed that PBP significantly protected skin cells against UVB-stimulated photodamage. PBP suppressed human epidermal keratinocyte (HaCaT cell) death by inhibiting apoptosis and reducing the level of intracellular reactive oxygen species. The intracellular reactive oxygen species level of HaCaT cells irradiated by UVB was reduced from 192.67% to 181.22%, 170.25%, and 160.48% by 25 µg/mL, 50 µg/mL, and 100 µg/mL PBP, respectively. In addition, PBP remarkably reduced UVB-induced human dermal fibroblast damage by suppressing oxidative damage, inhibiting collagen degradation, and attenuating inflammatory responses. These results indicate that PBP possesses photoprotective and anti-melanogenesis activities and suggest that PBP is a potential ingredient in the cosmetic industry.

Antioxidant, Antiviral, and Anti-Inflammatory Activities of Lutein-Enriched Extract of Tetraselmis Species.

Microalgae are proposed to have powerful applications for human health in the pharmaceutical and food industries. Tetraselmis species (sp.), which are green microalgae, were identified as a source of broad-spectrum health-promoting biological activities. However, the bioactivity of these species has not been elucidated. We aimed to confirm the antioxidant, antiviral, and anti-inflammatory effects of Tetraselmis sp. extract (TEE). TEE showed 2,2-diphenyl-1-picryl-hydrazyl-hydrate radical and hydrogen peroxide scavenging activities and reduced plaque formation in Vero E6 cells infected with vaccinia virus. TEE treatment also significantly inhibited nitric oxide (NO) production and improved cell viability in lipopolysaccharide (LPS)-induced RAW264.7 cells. These anti-inflammatory effects were further analyzed in LPS-induced RAW 264.7 cells and the zebrafish model. Further, TEE reduced induced NO synthase expression and proinflammatory cytokine release, including tumor necrosis factor-α, interleukin-6, and interleukin-1ß, through MAPKs and NF-κB-dependent mechanisms. Further analysis revealed that TEE increased the survival rate and reduced cell death and NO production in an LPS-stimulated zebrafish model. Further, high-performance liquid chromatography revealed a strong presence of the carotenoid lutein in TEE. Overall, the results suggest that lutein-enriched TEE may be a potent antioxidant, antiviral, and anti-inflammatory agent that could be sustainably utilized in industrial applications.

Age-related increase in caveolin-1 expression facilitates cell-to-cell transmission of α-synuclein in neurons.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease, with aging being considered the greatest risk factor for developing PD. Caveolin-1 (Cav-1) is known to participate in the aging process. Recent evidence indicates that prion-like propagation of misfolded α-synuclein (α-syn) released from neurons to neighboring neurons plays an important role in PD progression. In the present study, we demonstrated that cav-1 expression in the brain increased with age, and considerably increased in the brain of A53T α-syn transgenic mice. Cav-1 overexpression facilitated the uptake of α-syn into neurons and formation of additional Lewy body-like inclusion bodies, phosphorylation of cav-1 at tyrosine 14 was found to be crucial for this process. This study demonstrates the relationship between age and α-syn spread and will facilitate our understanding of the molecular mechanism of the cell-to-cell transmission of α-syn.

5-Bromoprotocatechualdehyde Combats against Palmitate Toxicity by Inhibiting Parkin Degradation and Reducing ROS-Induced Mitochondrial Damage in Pancreatic ß-Cells.

Pancreatic ß-cell loss is critical in diabetes pathogenesis. Up to now, no effective treatment has become available for ß-cell loss. A polyphenol recently isolated from Polysiphonia japonica, 5-Bromoprotocatechualdehyde (BPCA), is considered as a potential compound for the protection of ß-cells. In this study, we examined palmitate (PA)-induced lipotoxicity in Ins-1 cells to test the protective effects of BPCA on insulin-secreting ß-cells. Our results demonstrated that BPCA can protect ß-cells from PA-induced lipotoxicity by reducing cellular damage, preventing reactive oxygen species (ROS) overproduction, and enhancing glucose-stimulated insulin secretion (GSIS). BPCA also improved mitochondrial morphology by preserving parkin protein expression. Moreover, BPCA exhibited a protective effect against PA-induced ß-cell dysfunction in vivo in a zebrafish model. Our results provide strong evidence that BPCA could be a potential therapeutic agent for the management of diabetes.

A potential therapeutic combination for treatment of COVID-19: Synergistic effect of DPP4 and RAAS suppression.

COVID-19, caused by the novel coronavirus SARS-CoV-2, is an abbreviated name for coronavirus disease 2019. COVID-19 became a global pandemic in early 2020. It predominantly affects not only the upper and lower respiratory tract, but also multiple organs, including the kidney, heart, and brain. The mortality of COVID-19 patients is high in men and in elderly patients with age-related diseases such as hypertension and diabetes. The angiotensin converting enzyme-2 (ACE-2), a component in the renin-angiotensin-aldosterone system (RAAS), plays as cell surface receptors for SARS-CoV-2. A recent study proved that coronavirus SARS-CoV-2 also uses dipeptidyl peptidase-4 (DPP4, also known as adenosine deaminase complexing protein 2, CD26) as a co-receptor when entering cells. In addition, DPP4 is also implicated in the regulation of the immune response. Thus, the combination of DPP4 inhibition and suppression of ACE-2/RAAS may be a novel therapeutic strategy for combating this pandemic.

Diphlorethohydroxycarmalol Attenuates Palmitate-Induced Hepatic Lipogenesis and Inflammation.

Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease, encompassing a range of conditions caused by lipid deposition within liver cells, and is also associated with obesity and metabolic diseases. Here, we investigated the protective effects of diphlorethohydroxycarmalol (DPHC), which is a polyphenol isolated from an edible seaweed, Ishige okamurae, on palmitate-induced lipotoxicity in the liver. DPHC treatment repressed palmitate-induced cytotoxicity, triglyceride content, and lipid accumulation. DPHC prevented palmitate-induced mRNA and protein expression of SREBP (sterol regulatory element-binding protein) 1, C/EBP (CCAAT-enhancer-binding protein) α, ChREBP (carbohydrate-responsive element-binding protein), and FAS (fatty acid synthase). In addition, palmitate treatment reduced the expression levels of phosphorylated AMP-activated protein kinase (AMPK) and sirtuin (SIRT)1 proteins, and DPHC treatment rescued this reduction. Moreover, DPHC protected palmitate-induced liver toxicity and lipogenesis, as well as inflammation, and enhanced AMPK and SIRT1 signaling in zebrafish. These results suggest that DPHC possesses protective effects against palmitate-induced toxicity in the liver by preventing lipogenesis and inflammation. DPHC could be used as a potential therapeutic or preventive agent for fatty liver diseases.

5-Bromo-3,4-dihydroxybenzaldehyde from Polysiphonia morrowii attenuate IgE/BSA-stimulated mast cell activation and passive cutaneous anaphylaxis in mice.

The present study investigates the anti-allergic activity of the marine algal bromophenol, 3-bromo-4,5-dihydroxybenzaldehyde (BDB), isolated from Polysiphonia morrowii Harvey in immunoglobulin (Ig)E/bovine serum albumin (BSA)-stimulated mouse bone marrow-derived cultured mast cells (BMCMCs) and a passive cutaneous anaphylaxis (PCA) mice ear model. BDB effectively inhibited ß-hexosaminidase release (IC50 = 80.12 µM), in IgE/BSA-stimulated BMCMCs without a cytotoxic response. Also, BDB down-regulated the expression or secretion of cytokines, interleukin (IL)-1ß, IL-4, IL-5, IL-6, IL-10, IL-13, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α and the chemokine (thymus and activation-regulated chemokine (TARC). The above effects could be attributed to the dose-dependent decrease of FcεRI expression on the surface of BMCMCs and its stable IgE binding. Moreover, BDB suppressed the nuclear factor (NF)-κB and spleen tyrosine kinase (SYK)-linker for T-cell activation (LAT)-GRB2 associated binding protein 2 (Gab2) signaling axis activated by IgE/BSA stimulation. Furthermore, oral administration of BDB to IgE-sensitized mice effectively attenuated IgE-triggered PCA reaction. Collectively, the anti-allergic effects of BDB suggest its potential applicability as a candidate for in-depth test trials.

Protective Effect of Diphlorethohydroxycarmalol Isolated from Ishige okamurae Against Particulate Matter-Induced Skin Damage by Regulation of NF-κB, AP-1, and MAPKs Signaling Pathways In Vitro in Human Dermal Fibroblasts.

Particulate matters (PM), the main contributor to air pollution, have become a serious issue that threatens human's health. Skin is the largest organ in humans, as well as the primary organ exposed to PM. Overexposure of PM induces skin damage. Diphlorethohydroxycarmalol (DPHC), an algal polyphenol with the potential of skin protection, has been isolated from the edible brown seaweed Ishige okamurae. The purpose of the present study is to investigate the protective effect of DPHC against PM (ERM-CZ100)-induced skin damage in human dermal fibroblasts (HDF) cells. The results indicated that DPHC significantly and dose-dependently reduced intracellular reactive oxygen species generation in HDF cells. In addition, DPHC significantly induced collagen synthesis and inhibited collagenase activity in ERM-CZ100-stimulated HDF cells. Further study demonstrated that DPHC remarkably reduced the expression of human matrix metalloproteinases through regulation of nuclear factor kappa B, activator protein 1, and mitogen-activated protein kinases signaling pathways in ERM-CZ100-stimulated HDF cells. This study suggested that DPHC is a potential candidate to protect skins against PM-induced damage, and it could be used as an ingredient in pharmaceutical and cosmeceutical industries.

Direct differentiation of insulin-producing cells from human urine-derived stem cells.

The loss of pancreatic ß-cells is a cause of diabetes. Therefore, replacement of pancreatic ß-cells is a logical strategy for the treatment of diabetes, and the generation of insulin-producing cells (IPCs) from stem cells has been widely investigated as an alternative source for pancreatic ß-cells. Here, we isolated stem cells from human urine and investigated their differentiation potential into IPCs. We checked the expression of surface stem cell markers and stem cell transcription factors, and found that the isolated human urine-derived stem cells (hUDSCs) expressed the stem cell markers CD44, CD90, CD105 and stage-specific embryonic antigen (SSEA)-4. In addition, these cells expressed octamer binding transcription factor (Oct)4 and vimentin. hUDSCs could differentiate into adipocytes and osteocytes, as evidenced by Oil-red O staining and Alizarin Red S-staining of differentiated cells, respectively. When we directly differentiated hUDSCs into IPCs, the differentiated cells expressed mRNA for pancreatic transcription factors such as neurogenin (Ngn)3 and pancreatic and duodenal homeobox (Pdx)1. Differentiated IPCs expressed insulin and glucagon mRNA and protein, and these IPCs also secreted insulin in response to glucose stimulation. In conclusion, we found that hUDSCs can be directly differentiated into IPCs, which secrete insulin in response to glucose.

Radio-Protective Effects of Loliolus beka Gray Meat Consisted of a Plentiful Taurine Against Damages Caused by Gamma Ray Irradiation.

Gamma ray irradiation causes immune suppression, in which oxidative stress reduces cell viability and damages immune cells. In the present study, we investigated whether Loliolus beka gray meat (LBM), which contains large amounts of taurine, protects against damage of murine splenocytes by oxidative stress. An aqueous extract of LBM (LBMW) was prepared, which contained plentiful levels of taurine. LBMW improved cell viability of gamma ray-irradiated murine splenocytes, an effect that was associated with significant reduction in the production of reactive oxygen species (ROS). We also showed that the production of nitric oxide (NO) and ROS in gamma ray-irradiated zebrafish embryos, as well as the death of the embryos, were diminished by LBMW. These data suggest that the consumption of taurine-rich foods, such as LBM, may be used in the protection of cells against oxidative stress.

Indole-4-carboxaldehyde Isolated from Seaweed, Sargassum thunbergii, Attenuates Methylglyoxal-Induced Hepatic Inflammation.

Glucose degradation is aberrantly increased in hyperglycemia, which causes various harmful effects on the liver. Glyoxalase-1 (Glo-1) is a ubiquitous cellular enzyme that participates in the detoxification of methylglyoxal (MGO), a cytotoxic byproduct of glycolysis that induces protein modification (advanced glycation end-products, AGEs) and inflammation. Here, we investigated the anti-inflammatory effect of indole-4-carboxaldehyde (ST-I4C), which was isolated from the edible seaweed Sargassum thunbergii, on MGO-induced inflammation in HepG2 cells, a human hepatocyte cell line. ST-I4C attenuated the MGO-induced expression of inflammatory-related genes, such as tumor necrosis factor (TNF)-α and IFN-γ by activating nuclear factor-kappa B (NF-κB) without toxicity in HepG2 cells. In addition, ST-I4C reduced the MGO-induced AGE formation and the expression of the receptor for AGE (RAGE). Interestingly, both the mRNA and protein expression levels of Glo-1 increased following ST-I4C treatment, and the decrease in Glo-1 mRNA expression caused by MGO exposure was rescued by ST-I4C pretreatment. These results suggest that ST-I4C shows anti-inflammatory activity against MGO-induced inflammation in human hepatocytes by preventing an increase in the pro-inflammatory gene expression and AGE formation. Therefore, it represents a potential therapeutic agent for the prevention of hepatic steatosis.

Diphlorethohydroxycarmalol Attenuates Methylglyoxal-Induced Oxidative Stress and Advanced Glycation End Product Formation in Human Kidney Cells.

Diabetic nephropathy is the leading cause of end-stage renal disease in patients with diabetes mellitus. Oxidative stress has been shown to play an important role in pathogeneses of renal damage in diabetic patients. Here, we investigated the protective effect of diphlorethohydroxycarmalol (DPHC), which is a polyphenol isolated from an edible seaweed, Ishige okamurae, on methylglyoxal-induced oxidative stress in HEK cells, a human embryonic kidney cell line. DPHC treatment inhibited methylglyoxal- (MGO-) induced cytotoxicity and ROS production. DPHC activated the Nrf2 transcription factor and increased the mRNA expression of antioxidant and detoxification enzymes, consequently reducing MGO-induced advanced glycation end product formation. In addition, DPHC increased glyoxalase-1 mRNA expression and attenuated MGO-induced advanced glycation end product formation in HEK cells. These results suggest that DPHC possesses a protective activity against MGO-induced cytotoxicity in human kidney cells by preventing oxidative stress and advanced glycation end product formation. Therefore, it could be used as a potential therapeutic agent for the prevention of diabetic nephropathy.

Palmitate induces nitric oxide production and inflammatory cytokine expression in zebrafish.

Inflammation markers in zebrafish embryos reflect a toxic response that is common to other animal models and humans. Free fatty acids (FFAs) are known to cause damage in various tissues by inducing inflammation. In this study, we investigated whether a FFA (palmitate) induces inflammation in zebrafish embryos. Nitrous oxide (NO) production and cyclooxygenase-2 (COX-2) mRNA expression were increased in palmitate-treated zebrafish embryos in a dose-dependent manner. mRNA expression of pro-inflammatory cytokines, interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF- α), were also increased. Additionally, the mRNA expression of p65 nuclear factor-kB and I-kB-α were significantly increased after palmitate-treatment. Increased reactive oxygen species (ROS) expression was observed in palmitate-treated zebrafish embryos as well as pericardial edema. Additionally, mRNA expression of pro-inflammatory cytokines were increased in zebrafish liver and pancreas fed with palmitate-contained diet. Taken together, these results indicated that palmitate increases pro-inflammatory mediators in zebrafish embryos, suggesting that zebrafish could be an alternative animal model for inflammatory disease including diabetes.

Prion-like Propagation of α-Synuclein Is Regulated by the FcγRIIB-SHP-1/2 Signaling Pathway in Neurons.

Recent evidence of prion-like propagation of α-synuclein (α-syn) into neighboring neurons set up a paradigm to elucidate the mechanism of progression of Parkinson's disease (PD) and to develop therapeutic strategies. Here, we show that FcγRIIB expressed in neurons functions as a receptor for α-syn fibrils and mediates cell-to-cell transmission of α-syn. SHP-1 and 2 are activated downstream by α-syn fibrils through FcγRIIB and play an important role in cell-to-cell transmission of α-syn. Also, taking advantage of a co-culture system, we show that cell-to-cell transmission of α-syn induces intracellular Lewy body-like inclusion body formation and that the FcγRIIB/SHP-1/2 signaling pathway is involved in it. Therefore, the FcγRIIB-SHP-1/-2 signaling pathway may be a therapeutic target for the progression of PD. The in vitro system is an efficient tool for further high-throughput screening that can be used for developing a therapeutic intervention in PD.

Protective effect of fucoidan against AAPH-induced oxidative stress in zebrafish model.

Fucoidan, extracted from Ecklonia cava, has been extensively studied because of its wide biological activities. However, antioxidative activities have not been yet examined. Therefore we evaluated in vitro and in vivo studies on antioxidative activities of E. cava fucoidan (ECF). ECF exhibited more prominent effects in peroxyl radical scavenging activity, compared to the other scavenging activities. Thus, ECF was further evaluated for its protective ability against 2,2'-azobis dihydrochloride induced oxidative stress in Vero cells and ECF strongly reduced the AAPH-induced oxidative damage through scavenging intracellular reactive oxygen species. Furthermore, we evaluated protective effect of ECF against AAPH-induced oxidative stress in zebrafish model. ECF significantly reduced ROS generation, lipid peroxidation and cell death in zebrafish model. These findings indicate that ECF has antioxidant activities in vitro Vero cells and in vivo zebrafish model, even though ECF is not a polyphenol or flavonoid compound and does not contain benzene rings or conjugated structures.

Protective effects of phlorotannins against ultraviolet B radiation in zebrafish (Danio rerio).

Exposure to ultraviolet B (UV-B) radiation has been associated with a variety of adverse effects in all forms of life, including micro-organisms, plants, animals and humans. Ultraviolet B induces cell damage at the molecular level and consequently organisms must employ strategies to protect themselves from sunlight and to repair UV-B-induced cellular damage. In this study, the UV-B protective effects of four different phlorotannins isolated from a brown alga (Ecklonia cava) were determined using zebrafish (Danio rerio) as an in vivo model. Zebrafish embryos were pretreated with phlorotannins and exposed to UV-B (50 mJ/cm(2)). The heart rate, generation of reactive oxygen species and nitric oxide, cell death and hyperpigmentation were assessed in order to evaluate UV-B-induced photo-damage. Treatment of the embryos with the algal phorotannins reduced UV-B-induced reactive oxygen species and nitric oxide levels, protected against UV-B-induced cell death and significantly reduced hyperpigmentation. We therefore suggest that phlorotannins isolated from E. cava can protect against UV-B radiation. Editor Note. Readers of the journal may be unfamiliar with the use of zebrafish embryos in research studies. There is no indication in this article of an ethical review of the study. This is because the use of fish embryos in research, at least in the UK, is not subject to a licensing procedure if they are less than 5 days post fertilization (dpf). In this study the embryos were 2 dpf.

Inhibitory effect of diphlorethohydroxycarmalol on melanogenesis and its protective effect against UV-B radiation-induced cell damage.

In this study, potential inhibitory effect of 21 species of marine algae on melanogenesis was assessed via tyrosinase inhibitory effect. The Ishige okamurae extract tested herein evidenced profound tyrosinase inhibitory effect, compared to that exhibited by other marine algae extracts. Thus, I. okamurae was selected for use in further experiments, and was partitioned with different organic solvents. Profound tyrosinase inhibitory effect was detected in the ethyl acetate fraction, and the active compound was identified as the carmalol derivative, diphlorethohydroxycarmalol (DPHC), which evidenced higher levels of activity than that of commercial whitening agent. Intracellular reactive oxygen species (ROS) induced by ultraviolet (UV)-B radiation was reduced by the addition of DPHC and cell viability was dose-dependently increased. Moreover, DPHC demonstrated strong protective properties against UV-B radiation via damaged DNA tail length and morphological changes in fibroblast. Hence, these results indicate that DPHC isolated from I. okamurae has potential whitening effects and prominent protective effects on UV-B radiation-induced cell damages which might be used in pharmaceutical and cosmeceutical industries.

Effect of phlorotannins isolated from Ecklonia cava on melanogenesis and their protective effect against photo-oxidative stress induced by UV-B radiation.

In the present study, three kinds of phlorotannins, marine algal polyphenol, were isolated from a brown alga Ecklonia cava, and their inhibitory effect on melanogenesis as well as the protective effect against photo-oxidative stress induced by UV-B radiation was investigated. The effect on melanogenesis was evaluated via the inhibitory effects of tyrosinase and melanin synthesis. Among the phlorotannins, dieckol showed higher effect than that of the other phlorotannins in the both assays; especially the value of dieckol in the tyrosinase inhibition assay was relatively higher than that of a commercial tyrosinase inhibitor (kojic acid). The UV-B protection effect was evaluated via DCFH-DA, MTT, comet assays, and morphological changes in fibroblast. Intracellular ROS induced by UV-B radiation was reduced by the addition of phlorotannins and cell viability was dose-dependently increased. Moreover, dieckol demonstrated strong protective properties against UV-B radiation-induced DNA damage via damaged tail intensity and morphological changes in fibroblast. Hence, these results indicated that dieckol isolated from E. cava has potential whitening effects and prominent protective effects on UV-B radiation-induced cell damages, which might be used in pharmaceutical and cosmeceutical industries.

Polysiphonia japonica extract suppresses the Wnt/beta-catenin pathway in colon cancer cells by activation of NF-kappaB.

Abnormal activation of the Wnt/beta-catenin pathway and subsequent up-regulation of beta-catenin response transcription (CRT) are associated with the development of colon cancer. Thus, the Wnt/beta-catenin pathway is an attractive target for chemoprevention and treatment of this cancer. We used a cell-based screen to identify a methanol extract of Polysiphonia japonica (EPJ) that suppresses the Wnt/beta-catenin pathway without altering the level of beta-catenin protein and reduces the expression of cyclin D1, which is a known beta-catenin/T cell factor (TCF)-dependent gene. EPJ inhibited the growth of various colon cancer cells. In addition, EPJ induced the nuclear translocation of nuclear factor-kappaB (NF-kappaB) in SW480 colon cancer cells. Our findings suggest that EPJ attenuates Wnt/beta-catenin signaling via activation of NF-kappaB and can potentially be used as a chemopreventive agent against colon cancer.