Svetlana P. Ermakova

Structure, biological activity, and enzymatic transformation of fucoidans from the brown seaweeds.

Recent advances in the study of fucoidans, biologically active sulfated α‐L‐fucans of diverse structures and synthesized exclusively by marine organisms, are overviewed. Their structure, biological activity, the products of their enzymatic degradation and the different enzymes of degradation and modification are considered.

Sulfated polysaccharides from brown seaweeds Saccharina japonica and Undaria pinnatifida: isolation, structural characteristics, and antitumor activity

During the last decade brown seaweeds attracted much attention as a source of polysaccharides, namely laminarans, alginic acids, and sulfated polysaccharides-fucoidans, with various structures and biological activities. In this study, sulfated polysaccharides were isolated from brown seaweeds Saccharina japonica (formerly named Laminaria) and Undaria pinnatifida and their antitumor activity was tested against human breast cancer T-47D and melanoma SK-MEL-28 cell lines. The sulfated polysaccharide form S. japonica was highly branched partially acetylated sulfated galactofucan, built up of (1→3)-α-L-fucose residues. The sulfated polysaccharide from U. pinnatifida was partially acetylated highly sulfated galactofucan consisting of (1→3)- or (1→3);(1→4)-α-L-fucose residues. Fucoidans from S. japonica and U. pinnatifida distinctly inhibited proliferation and colony formation in both breast cancer and melanoma cell lines in a dose-dependent manner. These results indicated that the use of sulfated polysaccharides from brown seaweeds S. japonica and U. pinnatifida might be a potential approach for cancer treatment.

Fucoidans from Brown Seaweeds Sargassum hornery, Eclonia cava, Costaria costata: Structural Characteristics and Anticancer Activity

Fucoidans were isolated by water extraction and ion-exchange chromatography from brown algae Eclonia cava, Sargassum hornery, and Costaria costata collected near of Korean coasts. The structures of fucoidans were investigated. Fucoidan from E. cava was mixture of sulfated rhamnogalactofucan and galactofucan. Fucoidan from C. costata was a sulfated galactofucan. Fucoidan isolated from S. hornery was separated into three fractions: a homofucan sulfate, a homofucan but without sulfate groups, and a sulfated rhamnofucan. The results clearly showed that fucoidans play an inhibitory role in colony formation in human melanoma and colon cancer cells and may be effective antitumor agents.

Anticancer and cancer preventive properties of marine polysaccharides: some results and prospects.

Many marine-derived polysaccharides and their analogues have been reported as showing anticancer and cancer preventive properties. These compounds demonstrate interesting activities and special modes of action, differing from each other in both structure and toxicity profile. Herein, literature data concerning anticancer and cancer preventive marine polysaccharides are reviewed. The structural diversity, the biological activities, and the molecular mechanisms of their action are discussed.

Inhibitory effects of fucoidan on activation of epidermal growth factor receptor and cell transformation in JB6 Cl41 cells

Algal fucoidan is a marine sulfated polysaccharide with a wide variety of biological activities including anti-thrombotic, anti-inflammatory, and anti-tumor activities. In this study, we tested the hypothesis that fucoidan may suppress neoplastic cell transformation by inhibiting the phosphorylation of epidermal growth factor receptor (EGFR) in mouse epidermal JB6 Cl41 cells. Our results provided the first evidence that fucoidan from Laminaria guryanovae exerted a potent inhibitory effect on EGF-induced phosphorylation of EGFR. Consistent with its inhibitory action on phosphorylation of EGFR, fucoidan clearly suppressed the phosphorylation of extracellular signal-regulated kinase or c-jun N-terminal kinases induced by EGF. Moreover, EGF-induced the c-fos and c-jun transcriptional activities were inhibited by fucoidan, resulting to suppressing of activator protein-1 (AP-1) activity and cell transformation induced by EGF. Taken together, these results indicate that fucoidan might exert chemopreventive effects through the inhibition of phosphorylation of the EGFR.

Structural Characteristics and Anticancer Activity of Fucoidan from the Brown Alga Sargassum mcclurei

Three different fucoidan fractions were isolated and purified from the brown alga, Sargassum mcclurei. The SmF1 and SmF2 fucoidans are sulfated heteropolysaccharides that contain fucose, galactose, mannose, xylose and glucose. The SmF3 fucoidan is highly sulfated (35%) galactofucan, and the main chain of the polysaccharide contains a →3)-α-l-Fucp(2,4SO3−)-(1→3)-α-l-Fucp(2,4SO3−)-(1→ motif with 1,4-linked 3-sulfated α-l-Fucp inserts and 6-linked galactose on reducing end. Possible branching points include the 1,2,6- or 1,3,6-linked galactose and/or 1,3,4-linked fucose residues that could be glycosylated with terminal β-d-Galp residues or chains of alternating sulfated 1,3-linked α-l-Fucp and 1,4-linked β-d-Galp residues, which have been identified in galactofucans for the first time. Both α-l-Fucp and β-d-Galp residues are sulfated at C-2 and/or C-4 (and some C-6 of β-d-Galp) and potentially the C-3 of terminal β-d-Galp, 1,4-linked β-d-Galp and 1,4-linked α-l-Fucp residues. All fucoidans fractions were less cytotoxic and displayed colony formation inhibition in colon cancer DLD-1 cells. Therefore, these fucoidan fractions are potential antitumor agents.

Structure, enzymatic transformation and anticancer activity of branched high molecular weight laminaran from brown alga Eisenia bicyclis

The structure of high molecular weight laminaran from brown alga Eisenia bicyclis was investigated by chemical and enzymatic methods, NMR spectroscopy and mass spectrometry. The laminaran from E. bicyclis was characterized as 1,3;1,6-β-D-glucan with the high content of 1,6-linked glucose residues (ratio of bonds 1,3:1,6=1.5:1), which are both in the branches and in the main chain of the laminaran. The degree of polymerization of fragments, building from 1,3-linked glucose residues with single glucose branches at C-6 or without it, was no more than four glucose residues. The main part of 1,3-linked glucose blocks was builded from disaccharide fragments. 1,6-Linked glucose residues were localized basically on non-reduced ends of molecules. The degree of polymerization of 1,6-linked blocks was not greater than three glucose residues. Laminaran contained laminarioligosaccharides, gentiobiose, gentiotriose and single glucose residues in the branches at the C-6. Laminaran and its products of enzymatic hydrolysis inhibited a colony formation of human melanoma SK-MEL-28 and colon cancer DLD-1 cells. It was shown that decreasing the molecular weight of native laminaran to a determined limit (degree of polymerization 9-23) and increasing the content of 1,6-linked glucose residues increased the anticancer effect. Therefore, they may be perspective antitumor agents.

The fucoidans from brown algae of Far-Eastern seas: Anti-tumor activity and structure–function relationship

The sulfated polysaccharides from brown algae - the fucoidans - are known to be a topic of numerous studies, due to their beneficial biological activities including anti-tumour activity. In this study the effect of fucoidans isolated from brown algae Saccharina cichorioides, Fucus evanescens, and Undaria pinnatifida on the proliferation, neoplastic transformation, and colony formation of mouse epidermal cells JB6 Cl41, human colon cancer DLD-1, breast cancer T-47D, and melanoma RPMI-7951 cell lines was investigated. The algal fucoidans specifically and markedly suppressed the proliferation of human cancer cells with less cytotoxic effects against normal mouse epidermal cells. The highly sulfated (1→3)-α-l-fucan from S. cichorioides was found to be vitally important in the inhibition of EGF-induced neoplastic transformation of JB6 Cl41 cells. In colony formation assay the fucoidans from different species of brown algae showed selective anti-tumour activity against different types of cancer, which depended on unique structures of the investigated polysaccharides. These results provide evidence for further exploring the use of the fucoidans from S. cichorioides, F. evanescens, and U. pinnatifida as novel chemotherapeutics against different types of cancer.

Fucoidan inhibits UVB-induced MMP-1 promoter expression and down regulation of type I procollagen synthesis in human skin fibroblasts

UVB reduces type I procollagen levels and increases matrix metalloproteinases-1 (MMP-1) levels in human skin and plays a major role in the process of photoaging. We previously reported that fucoidan inhibits UVB-induced MMP-1 expression at the protein and mRNA levels in human skin fibroblasts (HS68). Yet, the effects of fucoidan on UVB-induced MMP-1 promoter activity and type I procollagen have not been investigated. In this study, we assessed the effects of fucoidan on the inhibition of MMP-1 promoter activity and on the increase of type I procollagen synthesis in human skin fibroblasts. Fucoidan treatment significantly inhibited MMP-1 promoter activity compared to UVB irradiation alone. Fucoidan treatment also increased type I procollagen mRNA and protein expression in a dose-dependent manner compared to the control. Our data indicate that fucoidan may prevent UVB-induced MMP-1 expression and inhibit down-regulation of type I procollagen synthesis. We suggest that fucoidan may be a potential therapeutic agent to prevent and treat skin photoaging.

Effect of Costaria costata Fucoidan on Expression of Matrix Metalloproteinase-1 Promoter, mRNA, and Protein

Fucoidans are sulfated fucosylated polymers from brown algae cell walls. We assessed the inhibitory effects of Costaria costata fucoidan on UVB-induced MMP-1 promoter, mRNA, and protein expression in vitro using the immortalized human keratinocyte (HaCaT) cell line. Pretreatment with fucoidan significantly inhibited MMP-1 protein expression compared to UVB irradiation alone. Fucoidan significantly reduced MMP-1 mRNA expression and inhibited UVB-induced MMP-1 promoter activity by 37.3%, 53.3%, and 58.5% at 0.01, 0.1, and 1 microg/mL, respectively, compared to UVB irradiation alone. C. costata fucoidan may be a potential therapeutic agent to prevent and treat skin photoaging.