Abstract
This review deals with the pharmacology of nonstarch polysaccharides, namely fucoidans and chitosans, isolated from marine organisms. The work summarizes information from the international literature on the antitumor activities of native polysaccharides and their derivatives. The structures and physicochemical properties of these polysaccharides are described and the molecular mechanisms of their antitumor and antimetastatic effects are discussed.
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Adrianov, A.V., Current Problems in Marine Biodiversity Studies, Biol. Morya, 2004, vol. 30, no. 1, pp. 3–19 [Russ. J. Mar. Biol., 2004, vol. 30, no. 1, pp. S1–S16].
Alekseenko, T.V., Zhanaeva, S.Ya., Venediktova, A.A. et al., Protivoopukholevaya i antimetastaticheskaya aktivnost’ sulfatirovannogo polisakharida fukoidana, vydelennogo iz buroi vodorosli Okhotskogo morya Fucus evanescens (Antitumor and Antimetastatic Activity of the Sulfated Polysaccharide Fucoidan Extracted from the Brown Seaweed Fucus evanescens from the Sea of Okhotsk), Byull. Eksperim. Biol. i Med., 2007, vol. 143, no. 6, pp. 675–677.
Vischuk, O.S., Yermakova, S.P., Fam Dyuk Tin et al., Protivoopukholevaya aktivnost’ fukoidanov iz burykh vodoroslei (Antitumor Activity of Fucoidans from Brown Algae), Tikhookean. Med. Zhurnal, 2009, no. 3, pp. 92–95.
Zueva, Ye.P., Razina, T.G., Amosova, Ye.N. et al., Vliyanie khitozana s razlichnoi molekulyarnoi massoi na razvitie adenokartsinomy Erlikha i effektivnost’ tsiklofosfana u myshei (Effect of Chitosans with Different Molecular Weights on the Progress of Ehrlich’s Adenocarcinoma and Cyclophosphan Efficacy in Mice), Tikhookean. Med. Zhurnal, 2010, no. 2, pp. 82–84.
Queiroz, K.C., Assis, C.F., Medeiros, V.P., et al., Cytotoxicity Effect of Algal Polysaccharides on HL60 Cells, Biokhimiya, 2006, vol. 71, no. 12, pp. 1613–1617 [Biochemistry, 2006, vol. 71, no. 12, pp. 1312–1315].
Razina, T.G., Zueva, Ye.P., Amosova, Ye.N. et al., Vliyaniye fukoidana iz morskoi buroi vodorosli Laminaria japonica na razvitie adenokartsinomy Erlikha i kartsinomy legkikh L’yuis i effektivnost’ tsiklofosfana u myshei (Effect of Fucoidan from the Marine Brown Alga Laminaria japonica on the Progress of Ehrlich’s Adenocarcinoma and Lewis Lung Carcinoma and on Cyclophosphan Efficacy in Mice), Tikhookean. Med. Zhurnal, 2010, no. 2, pp. 36–39.
Stonik, V.A., Tolstikov, G.A., Prirodnye soedineniya i sozdanie otechestvennykh lekarstvennykh preparatov (Natural Compounds and Development of New Drugs in Russia), Vestnik DVO RAN, 2008, vol. 78, no. 8, pp. 675–687.
Khotimchenko, Yu.S., Yermak, I.M., Bednyak, A.Ye. et al., Farmakologiya nekrakhmalnykh polisakharidov (Pharmacology of Nonstarch Polysaccharides), Vestnik DVO RAN, 2005, no. 1, pp. 72–82.
Aisa, Y., Miyakawa, Y., Nakazato, T. et al., Fucoidan Induces Apoptosis of Human HS-sultan Cells Accompanied by Activation of Caspase-3 and Down-regulation of ERK Pathways, Am. J. Hematol., 2005, vol. 78, pp. 7–14.
Asp, N.-G.L., Classification and Methodology of Food Carbohydrates as Related to Nutritional Effects, Am. J. Clin. Nutr., 1995, vol. 61, pp. S930–S937.
Brunner, G., Reimbold, K., Meissauer, A. et al., Sulfated Glycosaminoglycans Enhance Tumor Cell Invasion in vitro by Stimulating Plasminogen Activation, Exp. Cell Res., 1998, vol. 239, pp. 301–310.
Burkitt, D.P., Epidemiology of Cancer of the Colon and Rectum, Cancer, 1971, vol. 28, pp. 3–13.
Carreno-Gomez, B., Duncan, R., Evaluation of the Biological Properties of Soluble Chitosan and Chitosan Microspheres, Int. J. Pharm., 1997, vol. 148, pp. 231–240.
Choi, E.M., Kim, A.J., Kim, Y.O., Hwang, J.K., Immunomodulating Activity of Arabinogalactan and Fucoidan in vitro, J. Med. Food., 2005, vol. 8, pp. 446–453.
Collén, P.N., Lemoine, M., Daniellou, R. et al., Enzymatic Degradation of κ-Carrageenan in Aqueous Solution, Biomacromolecules, 2009, vol. 10, pp. 1757–1767.
Coombe, D.R., Parish, C.R., Ramshaw, I.A., Snowden, J.M., Analysis of the Inhibition of Tumour Metastasis by Sulphated Polysaccharides, Int. J. Cancer, 1987, vol. 39, pp. 82–88.
Cumashi, A., Ushakova, N.A., Preobrazhenskaya, M.E. et al., A Comparative Study of the Anti-inflammatory, Anticoagulant, Antiangiogenic, and Antiadhesive Activities of Nine Different Fucoidans from Brown Seaweeds, Glycobiology, 2007, vol. 17, pp. 541–552.
d’Ayala, G.G., Malinconico, M., Laurienzo, P., Marine Derived Polysaccharides for Biomedical Applications: Chemical Modification Approaches, Molecules, 2008, vol. 13, pp. 2069–2106.
Do, H., Pyo, S., Sohn, E.H., Suppression of iNOS Expression by Fucoidan Is Mediated by Regulation of p38 MAPK, JAK/STAT, AP-1 and IRF-1, and Depends on Up-regulation of Scavenger Receptor B1 Expression in TNF-α- and IFN-γ-Stimulated C6 Glioma Cells, J. Nutr. Biochem., 2010, vol. 21,issue 8, pp. 671–679].
Duarte, M., Cardoso, M., Noseda, M., Structural Studies on Fucoidans from the Brown Seaweed Sargassum stenophyllum, Carbohydr. Res., 2001, vol. 333, pp. 281–293.
Ellouali, M., Boisson-Vidal, C., Durand, P., Jozefonvicz, J., Antitumor Activity of Low Molecular Weight Fucans Extracted from Brown Seaweed Ascophyllum nodosum, Anticancer Res., 1993, vol. 13, pp. 2011–2019.
Haneji, K., Matsuda, T., Tomita, M. et al., Fucoidan Extracted from Cladosiphon okamuranus Tokida Induces Apoptosis of Human T-Cell Leukemia Virus Type 1-Infected T-Cell Lines and Primary Adult T-Cell Leukemia Cells, Nutr. Cancer, 2005, vol. 52, pp. 189–201.
Harish Prashanth, K.V., Tharanathan, R.N., Depolymerized Products of Chitosan as Potent Inhibitors of Tumor-Induced Angiogenesis, Biochim. Biophys. Acta, 2005, vol. 1722, pp. 22–29.
Haroun-Bouhedja, F., Ellouali, M., Sinquin, C., Boisson-Vidal, C., Relationship between Sulfate Groups and Biological Activities of Fucans, Thromb Res., 2000, vol. 100, pp. 453–459.
Haroun-Bouhedja, F., Lindenmeyer, F., Lu, H. et al., In vitro Effects of Fucans on MDA-MB231 Tumor Cell Adhesion and Invasion, Anticancer Res., 2002, vol. 22, pp. 2285–2292.
Huang, R., Mendis, E., Rajapakse, N., Kim, S.K., Strong Electronic Charge as an Important Factor for Anticancer Activity of Chitooligosaccharides (COS), Life Sci., 2006, vol. 78, pp. 2399–2408.
Hyun, J.-H., Kim, S.-C., Kang, J.-I. et al., Apoptosis Inducing Activity of Fucoidan in NCT-15 Colon Carcinoma Cells, Biol. Pharm. Bull., 2009, vol. 32, pp. 1760–1764.
Itoh, H., Noda, H., Amano, H. et al., Antitumor Activity and Immunological Properties of Marine Algal Polysaccharides, Especially Fucoidan, Prepared from Sargassum thunbergii of Phaeophyceae, Anticancer Res., 1993, vol. 13, pp. 2045–2052.
Itoh, H., Noda, H., Amano, H., Ito, H., Immunological Analysis of Lung Metastasis by Fucoidan (GIV-A) Prepared from Brown Seaweed Sargassum thunbergii, Anticancer Res., 1995, vol. 15, pp. 1937–1947.
Kawabe, M., Futakuchi, M., Tamano, S. et al., Modifying Effects of Chitin, Chitosan and Their Related Compounds on 2-Amino-3,8-Dimethylimidazo[4,5-f]quinoxaline (MeIQx) in a Rat Medium-Term Hepatocarcinogenesis Model, and Their Post-initiation Effects in a Female Rat 2-Stage Multi-organ Carcinogenesis Model, Food Chem. Toxicol., 2008, vol. 46, pp. 2758–2763.
Kijjoa, A., Sawangwong, P., Drugs and Cosmetics from the Sea, Mar. Drugs, 2004, vol. 2, pp. 73–82.
Kim, M.M., Kim, S.K., Chitooligosaccharides Inhibit Activation and Expression of Matrix Metalloproteinase-2 in Human Dermal Fibroblasts, FEBS Lett., 2006, vol. 580, pp. 2661–2666.
Kimura, Y., Okuda, H., Prevention by Chitosan of Myelotoxicity, Gastrointestinal Toxicity and Immunocompetent Organic Toxicity Induced by 5-Flurouracil without Loss of Antitumor Activity in Mice, Jpn. J. Cancer Res., 1999, vol. 90, pp. 765–774.
Kobayashi, M., Watanabe, T., Suzuki, S., Suzuki, M., Effect of N-Acetylchitohexaose against Candida albicans Infection of Tumor-Bearing Mice, Microbiol. Immunol., 1990, vol. 34, pp. 413–426.
Koyanagi, S., Tanigawa, N., Nakagawa, H. et al., Oversulfation of Fucoidan Enhances Its Anti-angiogenic and Antitumor Activities, Biochem. Pharmacol., 2003, vol. 65, pp. 173–179.
Lee, J.K., Lim, H.S., Kim, J.H., Cytotoxic Activity of Aminoderivatized Cationic Chitosan Derivatives, Bioorg. Med. Chem. Lett., 2002, vol. 12, pp. 2949–2951.
Lee, N.Y., Ermakova, S.P., Zvyagintseva, T.N. et al., Inhibitory Effects of Fucoidan on Activation of Epidermal Growth Factor Receptor and Cell Transformation in JB6 Cl41 Cells, Food Chem. Toxicol., 2008a, vol. 46, pp. 1793–1800.
Lee, N.Y., Ermakova, S.P., Choi, H.K. et al., Fucoidan from Laminaria cichorioides Inhibits AP-1 Transactivation and Cell Transformation in the Mouse Epidermal JB6 Cells, Mol. Carcinog., 2008b, vol. 47, pp. 629–637.
Li, B., Lu, F., Wei, X., Zhao, R., Fucoidan: Structure and Bioactivity, Molecules, 2008, vol. 13, pp. 1671–1695.
Li-Feng, Q., Zi-Rong, X., Yan, L. et al., In vitro Effects of Chitosan Nanoparticles on Proliferation of Human Gastric Carcinoma Cell Line MGC803 Cells, World J. Gastroenterol., 2005, vol. 11, pp. 5136–5141.
Lin, S.Y., Chan, H.Y., Shen, F.H. et al., Chitosan Prevents the Development of AOM-Induced Aberrant Crypt Foci in Mice and Suppressed the Proliferation of AGS Cells by Inhibiting DNA Synthesis, J. Cell Biochem., 2007, vol. 100, pp. 1573–1580.
Liu, J.M., Bignon, J., Haroun-Bouhedja, F. et al., Inhibitory Effect of Fucoidan on the Adhesion of Adenocarcinoma Cells to Fibronectin, Anticancer Res., 2005, vol. 25, pp. 2129–2133.
Liu, J.M., Haroun-Bouhedja, F., Boisson-Vidal, C., Analysis of the in vitro Inhibition of Mammary Adenocarcinoma Cell Adhesion by Sulphated Polysaccharides, Anticancer Res., 2000, vol. 20, pp. 3265–3271.
Maeda, Y., Kimura, Y., Antitumor Effects of Various Low-Molecular-Weight Chitosans Are due to Increased Natural Killer Activity of Intestinal Intraepithelial Lymphocytes in Sarcoma 180-Bearing Mice, J. Nutr., 2004, vol. 134, pp. 945–950.
Maruyama, H., Tamauchi, H., Hashimoto, M., Nakano, T., Antitumor Activity and Immune Response of Mekabu Fucoidan Extracted from Sporophyll of Undaria pinnatifida, In Vivo, 2003, vol. 17, pp. 245–249.
Maruyama, H., Tamauchi, H., Iizuka, M., Nakano, T., The Role of NK Cells in Antitumor Activity of Dietary Fucoidan from Undaria pinnatifida Sporophylls (Mekabu), Planta Med., 2006, vol. 72, pp. 1415–1417.
Nagamine, T., Hayakawa, K., Kusakabe, T. et al., Inhibitory Effect of Fucoidan on Huh7 Hepatoma Cells through Downregulation of CXCL12, Nutr. Cancer, 2009, vol. 61, pp. 340–347.
Nam, K.-S., Kim, M.-K., Shon, Y.-H., Chemopreventive Effect of Chitosan Oligosaccharide against Colon Carcinogenesis, J. Microbiol. Biotechnol., 2007, vol. 17, pp. 1546–1549.
Nam, K.-S., Shon, Y.-H., Suppression of Metastasis of Human Breast Cancer Cells by Chitosan Oligosaccharide, J. Microbiol. Biotechnol., 2009, vol. 19, pp. 629–633.
Nishimura, K., Nishimura, S., Nishi, N. et al., Immunological Activity of Chitin and Its Derivates, Vaccine, 1984, vol. 2, pp. 93–99.
Nishino, T., Nishioka, C., Ura, H., Isolation and Partial Characterization of a Novel Amino Sugar-Containing Fucan Sulfate from Commercial Fucus vesiculosus Fucoidan, Carbohydr. Res., 1994, vol. 255, pp. 224–231.
Pilchenkov, A., Zavelevich, M., Imbs, T. et al., Sensitization of Human Malignant Lymphoid Cells to Etoposide by Fucoidan, a Brown Seaweed Polysaccharide, Exp. Oncol., 2007, vol. 29, pp. 181–185.
Pomin, V.H., Mouräo, P.A.S., Structure, Biology, Evolution, and Medical Importance of Sulfated Fucans and Galactans, Glycobiology, 2008, vol. 18, pp. 1016–1027.
Qin, C.Q., Du, Y.M., Xiao, L. et al., Enzymic Preparations of Water-Soluble Chitosan and Their Antitumor Activity, Int. J. Biol. Macromol., 2002, vol. 31, pp. 111–117.
Rajapakse, N., Kim, M.-M., Mendis, E. et al., Carboxylated Chitooligosaccharides (CCOS) Inhibit MMP-9 Expression in Human Fibrosarcoma Cells via Downregulation of AP-1, Biochim. Biophys. Acta, 2006, vol. 1760, pp. 1780–1788.
Rao, J.S., Molecular Mechanisms of Glioma Invasiveness: the Role of Proteases, Nat. Rev. Cancer, 2003, vol. 3, pp. 489–501.
Rinaudo, M., Chitin and Chitosan: Properties and Applications, Prog. Polym. Sci., 2006, vol. 31, pp. 603–632.
Riou, D., Colliec-Jouault, S., Pinczon du Sel, D. et al., Antitumor and Antiproliferative Effects of a Fucan Extracted from Ascophyllum nodosum against a Non-Small-Cell Bronchopulmonary Carcinoma Line, Anticancer Res., 1996, vol. 16, pp. 1213–1218.
Roszkowsky, W., Beuth, J., Ko, H.L. et al., Blocking of Lectin-like Adhesion Molecules on Pulmonary Cells Inhibits Lung Sarcoma L-1 Colonization in BALB/c-Mice, Experientia, 1989, vol. 45, pp. 584–588.
Saiki, I., Murata, J., Nakajima, M. et al., Inhibition by Sulfated Chitin Derivatives of Invasion through Extracellular Matrix and Enzymatic Degradation by Metastatic Melanoma Cells, Cancer Res., 1990, vol. 50, pp. 3631–3637.
Seo, W.G., Pae, H.O., Kim, N.Y. et al., Synergistic Cooperation between Water-Soluble Chitosan Oligomers and Interferon-γ for Induction of Nitric Oxide Synthesis and Tumoricidal Activity in Murine Peritoneal Macrophages, Cancer Lett., 2000, vol. 159, pp. 189–195.
Shahidi, F., Abuzaytoun, R., Chitin, Chitosan, and Co-products: Chemistry, Production, Applications, and Health Effects, Adv. Food Nutr. Res., 2005, vol. 49, pp. 189–195.
Shen, K.-T., Chen, M.-X., Chan, H.-Y. et al., Inhibitory Effects of Chitooligosaccharides on Tumor Growth and Metastasis, Food Chem. Toxicol., 2009, vol. 47, pp. 1864–1871.
Shi, Z.Y., Guo, Y.Z., Wang, Z., Pharmacological Activity of Fucoidan from Laminaria japonica, J. Shanghai Fish. Univ., 2000, vol. 9, pp. 268–271.
Singla, A.K., Chawla, M., Chitosan: Some Pharmaceutical and Biological Aspects—an Update, J. Pharm. Pharmacol., 2001, vol. 53, pp. 1047–1067.
Soeda, S., Ishida, S., Shimeno, H., Nagamatsu, A., Inhibitory Effect of Oversulfated Fucoidan on Invasion through Reconstituted Basement Membrane by Murine Lewis Lung Carcinoma, Jpn. J. Cancer Res., 1994. vol. 85, pp. 1144–1150.
Teas, J., The Dietary Intake of Laminaria, a Brown Seaweed, and Breast Cancer Prevention, Nutr. Cancer, 1983, vol. 4, pp. 217–222.
Torzsas, T.L., Kendall, C.W., Sugano, M. et al., The Influence of High and Low Molecular Weight Chitosan on Colonic Cell Proliferation and Aberrant Crypt Foci Development in CF1 Mice, Food Chem. Toxicol., 1996, vol. 34, pp. 73–77.
Usui, T., Isolation of Highly Purified Fucoidan from Eisenia bicyclics and Its Anticoagulant and Antitumor Activities, Agric. Biol. Chem., 1980, vol. 44, pp. 1965–1966.
Yamamoto, I., Takahashi, M., Suzuki, T. et al., Antitumor Effect of Seaweeds. IV. Enhancement of Antitumor Activity by Sulfation of a Crude Fucoidan Fraction from Sargassum kjellmanianum, Jpn. J. Exp. Med., 1984, vol. 54, pp. 143–151.
Yamazaki-Miyamoto, Y., Yamazaki, M. et al., Fucoidan Induces Apoptosis through Activation of Caspase-8 on Human Breast Cancer MCF-7 Cells, J. Agric. Food Chem., 2009, vol. 57, pp. 8677–8682.
Yang, C., Chung, D., Shin, I.S. et al., Effects of Molecular Weight and Hydrolysis Conditions on Anticancer Activity of Fucoidans from Sporophyll of Undaria pinnatifida, Int. J. Biol. Macromol., 2008, vol. 43, pp. 433–437.
Yang, Y.J., Nam, S.J., Kong, G., Kim, M.K., A Case-Control Study on Seaweed Consumption and the Risk of Breast Cancer, Brit. J. Nutr., 2009, vol. 8, pp. 1–9.
Ye, J., Li, Y., Teruya, K. et al., Enzyme-Digested Fucoidan Extracts Derived from Seaweed Mozuku of Cladosiphon novae-caledoniae Kylin Inhibit Invasion and Angiogenesis of Tumor Cells, Cytotechnology, 2005, vol. 47, pp. 117–126.
Zaharoff, D.A., Hoffman, B.S., Hooper, H.B. et al., Intravesical Immunotherapy of Superficial Bladder Cancer with Chitosan/Interleukin-12, Cancer Res., 2009, vol. 69, pp. 6192–6199.
Zhuang, C., Itoh, H., Mizuno, T., Ito, H., Antitumor Active Fucoidan from the Brown Seaweed, Umitoranoo (Sargassum thunbergii), Biosci. Biotechnol. Biochem., 1995, vol. 59, pp. 563–567.
Zvyagintseva, T.N., Shevchenko, N.M., Popivnich, I.B., A New Procedure for the Separation of Water-Soluble Polysaccharides from Brown Seaweeds, Carbohydr. Res., 1999, vol. 322, pp. 32–39.
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Khotimchenko, Y.S. Antitumor properties of nonstarch polysaccharides: Fucoidans and chitosans. Russ J Mar Biol 36, 321–330 (2010). https://doi.org/10.1134/S1063074010050019
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DOI: https://doi.org/10.1134/S1063074010050019