Fucoidan as a marine anticancer agent in preclinical development

Marine Drugs

Volumn 12, Issue 2, 2014, Pages 851-870

  Kwak, Jong Young ^a  

^a Dong A University   (South Korea)

Author keywords

Antiangiogenesis; Anticancer; Anticancer immunity; Fucoidan; Preclinical

Indexed keywords

CISPLATIN; FUCOIDIN; GAMMA INTERFERON; HLA DR ANTIGEN; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 12P70; INTERLEUKIN 5; INTERLEUKIN 8; PACLITAXEL; SCAVENGER RECEPTOR A; SCAVENGER RECEPTOR B; TAMOXIFEN; TUMOR NECROSIS FACTOR ALPHA; VASCULOTROPIN;

ANTIANGIOGENIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; APOPTOSIS; BREAST CANCER; CANCER CELL CULTURE; CANCER IMMUNOTHERAPY; CANCER INHIBITION; CANCER PREVENTION; COLITIS; CYTOKINE PRODUCTION; CYTOKINE RESPONSE; DENDRITIC CELL; DRUG POTENTIATION; DRUG RESEARCH; DRUG STRUCTURE; HEART INFARCTION; HEMATOPOIETIC STEM CELL; HUMAN; IMMUNOMODULATION; IMMUNOSTIMULATION; IN VITRO STUDY; IN VIVO STUDY; ISCHEMIA; LEISHMANIASIS; LEUKEMIA; LEWIS CARCINOMA; LIVER CELL CARCINOMA; LIVER FIBROSIS; LIVER INJURY; LYMPHOMA; METASTASIS INHIBITION; NATURAL KILLER CELL MEDIATED CYTOTOXICITY; NEUROTOXICITY; NONHUMAN; PLASMACYTOMA; PLEURA DISEASE; PNEUMONIA; REPERFUSION INJURY; REVIEW; SARCOMA; TUMOR VASCULARIZATION; TUMOR XENOGRAFT;

ANIMALS; ANTINEOPLASTIC AGENTS; DISEASE MODELS, ANIMAL; DRUG EVALUATION, PRECLINICAL; HUMANS; NEOPLASMS; NEOVASCULARIZATION, PATHOLOGIC; POLYSACCHARIDES; SEAWEED;

EID: 84896717589     PISSN: None     EISSN: 16603397     Source Type: Journal    
DOI: 10.3390/md12020851     Document Type: Review

References (114)

1. Pomin, V.H.; Mourão, P.A. Structure, biology, evolution, and medical importance of sulfated fucans and galactans. Glycobiology 2008, 18, 1016-1027.
2. Fitton, J.H. Therapies from fucoidan; multifunctional marine polymers. Mar. Drugs 2011, 9, 1731-1760.
3. Pomin, V.H. Fucanomics and galactanomics: Current status in drug discovery, mechanisms of action and role of the well-defined structures. Biochim. Biophys. Acta 2012, 1820, 1971-1979.
4. Berteau, O.; Mulloy, B. Sulfated fucans, fresh perspectives: Structures, functions, and biological properties of sulfated fucans and an overview of enzymes active towards this class of polysaccharide. Glycobiology 2003, 13, 29-40.
5. Senthilkumar, K.; Manivasagan, P.; Venkatesan, J.; Kim, S.K. Brown seaweed fucoidan: Biological activity and apoptosis, growth signaling mechanism in cancer. Int. J. Biol. Macromol. 2013, 60, 366-374.
6. Kim, M.H.; Joo, H.G. Immunostimulatory effects of fucoidan on bone marrow-derived dendritic cells. Immunol. Lett. 2008, 115, 138-143.
7. Yang, M.; Ma, C.; Sun, J.; Shao, Q.; Gao, W.; Zhang, Y.; Li, Z.; Xie, Q.; Dong, Z.; Qu, X. Fucoidan stimulation induces a functional maturation of human monocyte-derived dendritic cells. Int. Immunopharmacol. 2008, 8, 1754-1760.
8. Jin, J.O.; Park, H.Y.; Xu, Q.; Park, J.I.; Zvyagintseva, T.; Stonik, V.A.; Kwak, J.Y. Ligand of scavenger receptor class A indirectly induces maturation of human blood dendritic cells via production of tumor necrosis factor-α. Blood 2009, 113, 5839-5847.
9. Hu, Y.; Cheng, S.C.; Chan, K.T.; Ke, Y.; Xue, B.; Sin, F.W.; Zeng, C.; Xie, Y. Fucoidin enhances dendritic cell-mediated T-cell cytotoxicity against NY-ESO-1 expressing human cancer cells. Biochem. Biophys. Res. Commun. 2010, 392, 329-334.
10. Ale, M.T.; Maruyama, H.; Tamauchi, H.; Mikkelsen, J.D.; Meyer, A.S. Fucoidan from Sargassum sp. and Fucus vesiculosus reduces cell viability of lung carcinoma and melanoma cells in vitro and activates natural killer cells in mice in vivo. Int. J. Biol. Macromol. 2011, 49, 331-336.
11. Azuma, K.; Ishihara, T.; Nakamoto, H.; Amaha, T.; Osaki, T.; Tsuka, T.; Imagawa, T.; Minami, S.; Takashima, O.; Ifuku, S.; Morimoto, M.; et al. Effects of oral administration of fucoidan extracted from Cladosiphon okamuranus on tumor growth and survival time in a tumor-bearing mouse model. Mar. Drugs 2012, 10, 2337-2348.
12. + cells. Exp. Hematol. 2007, 35, 989-994.
13. Irhimeh, M.R.; Fitton, J.H.; Lowenthal, R.M. Pilot clinical study to evaluate the anticoagulant activity of fucoidan. Blood Coagul. Fibrinolysis 2009, 20, 607-610.
14. Myers, S.P.; O'Connor, J.; Fitton, J.H.; Brooks, L.; Rolfe, M.; Connellan, P.; Wohlmuth, H.; Cheras, P.A.; Morris, C. A combined phase I and II open label study on the effects of a seaweed extract nutrient complex on osteoarthritis. Biologics 2010, 4, 33-44.
15. Myers, S.P.; O'Connor, J.; Fitton, J.H.; Brooks, L.; Rolfe, M.; Connellan, P.; Wohlmuth, H.; Cheras, P.A.; Morris, C. A combined Phase I and II open-label study on the immunomodulatory effects of seaweed extract nutrient complex. Biologics 2011, 5, 45-60.
16. Kusaykin, M.; Bakunina, I.; Sova, V.; Ermakova, S.; Kuznetsova, T.; Besednova, N.; Zaporozhets, T.; Zvyagintseva, T. Structure, biological activity, and enzymatic transformation of fucoidans from the brown seaweeds. Biotechnol. J. 2008, 3, 904-915.
17. Jin, J.O.; Song, M.G.; Kim, Y.N.; Park, J.I.; Kwak, J.Y. The mechanism of fucoidan-induced apoptosis in leukemic cells: Involvement of ERK1/2, JNK, glutathione, and nitric oxide. Mol. Carcinog. 2010, 49, 771-782.
18. Park, H.S.; Hwang, H.J.; Kim, G.Y.; Cha, H.J.; Kim, W.J.; Kim, N.D.; Yoo, Y.H.; Choi, Y.H. Induction of apoptosis by fucoidan in human leukemia U937 cells through activation of p38 MAPK and modulation of Bcl-2 family. Mar. Drugs 2013, 11, 2347-2364.
19. Zhang, Z.; Teruya, K.; Eto, H.; Shirahata, S. Fucoidan extract induces apoptosis in MCF-7 cells via a mechanism involving the ROS-dependent JNK activation and mitochondria-mediated pathways. PLoS One 2011, 6, e27441.
20. Park, H.S.; Kim, G.Y.; Nam, T.J.; Kim, N.D.; Choi, Y.H. Antiproliferative activity of fucoidan was associated with the induction of apoptosis and autophagy in AGS human gastric cancer cells. J. Food Sci. 2011, 76, T77-T83.
21. Boo, H.J.; Hyun, J.H.; Kim, S.C.; Kang, J.I.; Kim, M.K.; Kim, S.Y.; Cho, H.; Yoo, E.S.; Kang, H.K. Fucoidan from Undaria pinnatifida induces apoptosis in A549 human lung carcinoma cells. Phytother. Res. 2011, 25, 1082-1086.
22. Boo, H.J.; Hong, J.Y.; Kim, S.C.; Kang, J.I.; Kim, M.K.; Kim, E.J.; Hyun, J.W.; Koh, Y.S.; Yoo, E.S.; Kwon, J.M.; et al. The anticancer effect of fucoidan in PC-3 prostate cancer cells. Mar. Drugs 2013, 11, 2982-2999.
23. Yang, L.; Wang, P.; Wang, H.; Li, Q.; Teng, H.; Liu, Z.; Yang, W.; Hou, L.; Zou, X. Fucoidan derived from Undaria pinnatifida induces apoptosis in human hepatocellular carcinoma SMMC-7721 cells via the ROS-mediated mitochondrial pathway. Mar. Drugs 2013, 11, 1961-1976.
24. Xue, M.; Ge, Y.; Zhang, J.; Wang, Q.; Hou, L.; Liu, Y.; Sun, L.; Li, Q. Anticancer properties and mechanisms of fucoidan on mouse breast cancer in vitro and in vivo. PLoS One 2012, 7, e43483.
25. Thinh, P.D.; Menshova, R.V.; Ermakova, S.P.; Anastyuk, S.D.; Ly, B.M.; Zvyagintseva, T.N. Structural characteristics and anticancer activity of fucoidan from the brown alga Sargassum mcclurei. Mar. Drugs 2013, 11, 1456-1476.
26. Kim, C.H.; Kim, C.G.; Kwak, J.Y. Role of scavenger receptor type A in the migration of dendritic cells and immunogenic antitumor effects by fucoidan. Dong-A University, Busan, Korea. 2014, unpublished work.
27. Alekseyenko, T.V.; Zhanayeva, S.Y.; Venediktova, A.A.; Zvyagintseva, T.N.; Kuznetsova, T.A.; Besednova, N.N.; Korolenko, T.A. Antitumor and antimetastatic activity of fucoidan, a sulfated polysaccharide isolated from the Okhotsk Sea Fucus evanescens brown alga. Bull. Exp. Biol. Med. 2007, 143, 730-732.
28. Zhu, C.; Cao, R.; Zhang, S.X.; Man, Y.N.; Wu, X.Z. Fucoidan inhibits the growth of hepatocellular carcinoma independent of angiogenesis. Evid. Based Complement. Alternat. Med. 2013, 2013, doi:10.1155/2013/692549.
29. Hsu, H.Y.; Lin, T.Y.; Hwang, P.A.; Tseng, L.M.; Chen, R.H.; Tsao, S.M.; Hsu, J. Fucoidan induces changes in the epithelial to mesenchymal transition and decreases metastasis by enhancing ubiquitin-dependent TGFβ receptor degradation in breast cancer. Carcinogenesis 2013, 34, 874-884.
30. Suresh, V.; Anbazhagan, C.; Thangam, R.; Senthilkumar, D.; Senthilkumar, N.; Kannan, S.; Rengasamy, R.; Palani, P. Stabilization of mitochondrial and microsomal function of fucoidan from Sargassum plagiophyllum in diethylnitrosamine induced hepatocarcinogenesis. Carbohydr. Polym. 2013, 92, 1377-1385.
31. Takeda, K.; Tomimori, K.; Kimura, R.; Ishikawa, C.; Nowling, T.K.; Mori, N. Anti-tumor activity of fucoidan is mediated by nitric oxide released from macrophages. Int. J. Oncol. 2012, 40, 251-260.
32. 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, 72, 1415-1417.
33. Koyanagi, S.; Tanigawa, N.; Nakagawa, H.; Soeda, S.; Shimeno, H. Oversulfation of fucoidan enhances its anti-angiogenic and antitumor activities. Biochem. Pharmacol. 2003, 65, 173-179.
34. Narazaki, M.; Segarra, M.; Tosato, G. Sulfated polysaccharides identified as inducers of neuropilin-1 internalization and functional inhibition of VEGF165 and semaphorin3A. Blood 2008, 111, 4126-4136.
35. Li, N.; Zhang, Q.; Song, J. Toxicological evaluation of fucoidan extracted from Laminaria japonica in Wistar rats. Food Chem. Toxicol. 2005, 43, 421-426.
36. Xue, M.; Ge, Y.; Zhang, J.; Liu, Y.; Wang, Q.; Hou, L.; Zheng, Z. Fucoidan inhibited 4T1 mouse breast cancer cell growth in vivo and in vitro via downregulation of Wnt/β-catenin signaling. Nutr. Cancer 2013, 65, 460-468.
37. Luyt, C.E.; Meddahi-Pellé, A.; Ho-Tin-Noe, B.; Colliec-Jouault, S.; Guezennec, J.; Louedec, L.; Prats, H.; Jacob, M.P.; Osborne-Pellegrin, M.; Letourneur, D.; et al. Low-molecular-weight fucoidan promotes therapeutic revascularization in a rat model of critical hindlimb ischemia. J. Pharmacol. Exp. Ther. 2003, 305, 24-30.
38. Deux, J.F.; Meddahi-Pellé, A.; le Blanche, A.F.; Feldman, L.J.; Colliec-Jouault, S.; Brée, F.; Boudghène, F.; Michel, J.B.; Letourneur, D. Low molecular weight fucoidan prevents neointimal hyperplasia in rabbit iliac artery in-stent restenosis model. Arterioscler. Thromb. Vasc. Biol. 2002, 22, 1604-1609.
39. Yang, C.; Chung, D.; Shin, I.S.; Lee, H.; Kim, J.; Lee, Y.; You, S. Effects of molecular weight and hydrolysis conditions on anticancer activity of fucoidans from sporophyll of Undaria pinnatifida. Int. J. Biol. Macromol. 2008, 43, 433-437.
40. 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, 17, 245-249.
41. Lippitz, B.E. Cytokine patterns in patients with cancer: A systematic review. Lancet Oncol. 2013, 14, e218-e228.
42. Menges, M.; Rössner, S.; Voigtländer, C.; Schindler, H.; Kukutsch, N.A.; Bogdan, C.; Erb, K.; Schuler, G.; Lutz, M.B. Repetitive injections of dendritic cells matured with tumor necrosis factor α induce antigen-specific protection of mice from autoimmunity. J. Exp. Med. 2002, 195, 15-21.
43. Palucka, K.; Banchereau, J. Cancer immunotherapy via dendritic cells. Nat. Rev. Cancer 2012, 12, 265-277.
44. Tejpar, S.; Prenen, H.; Mazzone, M. Overcoming resistance to antiangiogenic therapies. Oncologist 2012, 17, 1039-1050.
45. Soeda, S.; Kozako, T.; Iwata, K.; Shimeno, H. Oversulfated fucoidan inhibits the basic fibroblast growth factor-induced tube formation by human umbilical vein endothelial cells: Its possible mechanism of action. Biochim. Biophys. Acta 2000, 1497, 127-134.
46. Manzo-Silberman, S.; Louedec, L.; Meilhac, O.; Letourneur, D.; Michel, J.B.; Elmadbouh, I. Therapeutic potential of fucoidan in myocardial ischemia. J. Cardiovasc. Pharmacol. 2011, 58, 626-632.
47. Foxall, C.; Wei, Z.; Schaefer, M.E.; Casabonne, M.; Fugedi, P.; Peto, C.; Castellot, J.J., Jr.; Brandley, B.K. Sulfated malto-oligosaccharides bind to basic FGF, inhibit endothelial cell proliferation, and disrupt endothelial cell tube formation. J. Cell. Physiol. 1996, 168, 657-667.
48. Chabut, D.; Fischer, A.-M.; Colliec-Jouault, S.; Laurendeau, I.; Matou, S.; Le Bonniec, B.; Helley, D. Low molecular weight fucoidan and heparin enhance the basic fibroblast growth factor-induced tube formation of endothelial cells through heparin sulfate-dependent α6 overexpression. Mol. Pharmcol. 2003, 64, 696-702.
49. Chabut, D.; Fischer, A.M.; Helley, D.; Colliec, S. Low molecular weight fucoidan promotes FGF-2-induced vascular tube formation by human endothelial cells, with decreased PAI-1 release and ICAM-1 downregulation. Thrombosis Res. 2004, 113, 93-95.
50. Liu, F.; Wang, J.; Chang, A.K.; Liu, B.; Yang, L.; Li, Q.; Wang, P.; Zou, X. Fucoidan extract derived from Undaria pinnatifida inhibits angiogenesis by human umbilical vein endothelial cells. Phytomedicine 2012, 19, 797-803.
51. Fréguin-Bouilland, C.; Alkhatib, B.; David, N.; Lallemand, F.; Henry, J.P.; Godin, M.; Thuillez, C.; Plissonnier, D. Low molecular weight fucoidan prevents neointimal hyperplasia after aortic allografting. Transplantation 2007, 83, 1234-1241.
52. Wang, Y.Q.; Miao, Z.H. Marine-derived angiogenesis inhibitors for cancer therapy. Mar. Drugs 2013, 11, 903-933.
53. Arfors, K.E.; Ley, K. Sulfated polysaccharides in inflammation. J. Lab. Clin. Med. 1993, 121, 201-202.
54. Lindbom, L.; Xie, X.; Raud, J.; Hedqvist, P. Chemoattractant-induced firm adhesion of leukocytes to vascular endothelium in vivo is critically dependent on initial leukocyte rolling. Acta Physiol. Scand. 1992, 146, 415-421.
55. Ley, K.; Linnemann, G.; Meinen, M.; Stoolman, L.M.; Gaehtgens, P. Fucoidin, but not yeast polyphosphomannan PPME, inhibits leukocyte rolling in venules of the rat mesentery. Blood 1993, 81, 177-185.
56. Shimaoka, M.; Ikeda, M.; Iida, T.; Taenaka, N.; Yoshiya, I.; Honda, T. Fucoidin, a potent inhibitor of leukocyte rolling, prevents neutrophil influx into phorbol-ester-induced inflammatory sites in rabbit lungs. Am. J. Respir. Crit. Care Med. 1996, 153, 307-311.
57. Hickey, M.J.; Reinhardt, P.H.; Ostrovsky, L.; Jones, W.M.; Jutila, M.A.; Payne, D.; Elliott, J.; Kubes, P. Tumor necrosis factor-α induces leukocyte recruitment by different mechanisms in vivo and in vitro. J. Immunol. 1997, 158, 3391-3400.
58. Granert, C.; Raud, J.; Waage, A.; Lindquist, L. Effects of polysaccharide fucoidin on cerebrospinal fluid interleukin-1 and tumor necrosis factor a in pneumococcal meningitis in the rabbit. Infect. Immun. 1999, 67, 2071-2074.
59. Bachelet, L.; Bertholon, I.; Lavigne, D.; Vassy, R.; Jandrot-Perrus, M.; Chaubet, F.; Letourneur, D. Affinity of low molecular weight fucoidan for P-selectin triggers its binding to activated human platelets. Biochim. Biophys. Acta 2009, 1790, 141-146.
60. Sweeney, E.A.; Priestley, G.V.; Nakamoto, B.; Collins, R.G.; Beaudet, A.L.; Papayannopoulou, T. Mobilization of stem/progenitor cells by sulfated polysaccharides does not require selectin presence. Proc. Natl. Acad. Sci. USA 2000, 97, 6544-6549.
61. Hidalgo, A.; Peired, A.J.; Weiss, L.A.; Katayama, Y.; Frenette, P.S. The integrin αMβ2 anchors hematopoietic progenitors in the bone marrow during enforced mobilization. Blood 2004, 104, 993-1001.
62. Frenette, P.S.; Weiss, L. Sulfated glycans induce rapid hematopoietic progenitor cell mobilization: Evidence for selectin-dependent and independent mechanisms. Blood 2000, 96, 2460-2468.
63. Sweeney, E.A.; Lortat-Jacob, H.; Priestley, G.V.; Nakamoto, B.; Papayannopoulou, T. Sulfated polysaccharides increase plasma levels of SDF-1 in monkeys and mice: Involvement in mobilization of stem/progenitor cells. Blood 2002, 99, 44-51.
64. Tanaka, K.; Ito, M.; Kodama, M.; Tomita, M.; Kimura, S.; Hoyano, M.; Mitsuma, W.; Hirono, S.; Hanawa, H.; Aizawa, Y. Sulfated polysaccharide fucoidan ameliorates experimental autoimmune myocarditis in rats. J. Cardiovasc. Pharmacol. Ther. 2011, 16, 79-86.
65. Kar, S.; Sharma, G.; Das, P.K. Fucoidan cures infection with both antimony-susceptible and -resistant strains of Leishmania donovani through Th1 response and macrophage-derived oxidants. Antimicrob. Chemother. 2011, 66, 618-625.
66. Maruyama, H.; Tamauchi, H.; Hashimoto, M.; Nakano, T. Suppression of Th2 immune responses by mekabu fucoidan from Undaria pinnatifida sporophylls. Int. Arch. Allergy Immunol. 2005, 137, 289-294.
67. Kang, G.H.; Yan, B.C.; Cho, G.S.; Kim, W.K.; Lee, C.H.; Cho, J.H.; Kim, M.; Kang, I.J.; Won, M.H.; Lee, J.C. Neuroprotective effect of fucoidin on lipopolysaccharide accelerated cerebral ischemic injury through inhibition of cytokine expression and neutrophil infiltration. J. Neurol. Sci. 2012, 318, 25-30.
68. Costa, M.F.; Nihei, J.; Mengel, J.; Henriques, M.G.; Penido, C. Requirement of L-selectin for γδ T lymphocyte activation and migration during allergic pleurisy: Co-relation with eosinophil accumulation. Int. Immunopharmacol. 2009, 9, 303-312.
69. Matsumoto, S.; Nagaoka, M.; Hara, T.; Kimura-Takagi, I.; Mistuyama, K.; Ueyama, S. Fucoidan derived from Cladosiphon okamuranus Tokida ameliorates murine chronic colitis through the down-regulation of interleukin-6 production on colonic epithelial cells. Clin. Exp. Immunol. 2004, 136, 432-439.
70. Zhang, X.W.; Liu, Q.; Thorlacius, H. Inhibition of selectin function and leukocyte rolling protects against dextran sodium sulfate-induced murine colitis. Scand. J. Gastroenterol. 2001, 36, 270-275.
71. Li, C.; Gao, Y.; Xing, Y.; Zhu, H.; Shen, J.; Tian, J. Fucoidan, a sulfated polysaccharide from brown algae, against myocardial ischemia-reperfusion injury in rats via regulating the inflammation response. Food Chem. Toxicol. 2011, 49, 2090-2095.
72. Granert, C.; Raud, J.; Xie, X.; Lindquist, L.; Lindbom, L. Inhibition of leukocyte rolling with polysaccharide fucoidin prevents pleocytosis in experimental meningitis in the rabbit. J. Clin. Investig. 1994, 93, 929-936.
73. Nervi, B.; Link, D.C.; DiPersio, J.F. Cytokines and hematopoietic stem cell mobilization. J. Cell. Biochem. 2006, 99, 690-705.
74. Zlotnik, A. New insights on the role of CXCR4 in cancer metastasis . J. Pathol. 2008, 215, 211-213.
75. Furusato, B.; Mohamed, A.; Uhlén, M.; Rhim, J.S. CXCR4 and cancer. Pathol. Int. 2010, 60, 497-505.
76. Teicher, B.A.; Fricker, S.P. CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clin. Cancer Res. 2010, 16, 2927-2931.
77. Amara, A.; Lorthioir, O.; Valenzuela, A.; Magerus, A.; Thelen, M.; Montes, M.; Virelizier, J.L.; Delepierre, M.; Baleux, F.; Lortat-Jacob, H.; et al. Stromal cell-derived factor-1α associates with heparan sulfates through the first β-strand of the chemokine. J. Biol. Chem. 1999, 274, 23916-23925.
78. Sadir, R.; Baleux, F.; Grosdidier, A.; Imberty, A.; Lortat-Jacob, H. Characterization of the stromal cell-derived factor-1α-heparin complex. J. Biol. Chem. 2001, 276, 8288-8296.
79. Lortat-Jacob, H.; Grosdidier, A.; Imberty, A. Structural diversity of heparan sulfate binding domains in chemokines. Proc. Natl. Acad. Sci. USA 2002, 99, 1229-1234.
80. Sweeney, E.A.; Papayannopoulou, T. Increase in circulating SDF-1 after treatment with sulphated glycans, the role of SDF-1 in mobilization. Ann. N. Y. Acad. Sci. 2001, 938, 48-52.
81. Peiser, L.S.; Gordon, S. The function of scavenger receptors expressed by macrophages and their role in the regulation of inflammation. Microbes Infect. 2001, 3, 149-159.
82. Tamura, Y.; Adachi, H.; Osuga, J.; Ohashi, K.; Yahagi, N.; Sekiya, M.; Okazaki, H.; Tomita, S.; Iizuka, Y.; Shimano, H.; et al. FEEL-1 and FEEL-2 are endocytic receptors for advanced glycation end products. J. Biol. Chem. 2003, 278, 12613-12617.
83. Berwin, B.; Delneste, Y.; Lovingood, R.V.; Post, S.R.; Pizzo, S.V. SREC-I, a type F scavenger receptor, is an endocytic receptor for calreticulin. J. Biol. Chem. 2004, 279, 51250-51257.
84. Brown, M.S.; Goldstein, J.L. Lipoprotein metabolism in the macrophage: Implications for cholesterol deposition in atherosclerosis. Annu. Rev. Biochem. 1983, 52, 223-261.
85. Platt, N.; Gordon, S. Is the class A macrophage scavenger receptor (SR-A) multifunctional? - The mouse's tale. J. Clin. Investig. 2001, 108, 649-654.
86. Wang, X.Y.; Facciponte, J.; Chen, X.; Subjeck, J.R.; Repasky, E.A. Scavenger receptor - A negatively regulates antitumor immunity. Cancer Res. 2007, 67, 4996-5002.
87. Becker, M.; Cotena, A.; Gordon, S.; Platt, N. Expression of the class A macrophage scavenger receptor on specific subpopulations of murine dendritic cells limits their endotoxin response. Eur. J. Immunol. 2006, 36, 950-960.
88. Seimon, T.A.; Obstfeld, A.; Moore, K.J.; Golenbock, D.T.; Tabas, I. Combinatorial pattern recognition receptor signaling alters the balance of life and death in macrophages. Proc. Natl. Acad. Sci. USA 2006, 103, 19794-19799.
89. Ben, J.; Jin, G.; Zhang, Y.; Ma, B.; Bai, H.; Chen, J.; Zhang, H.; Gong, Q.; Zhou, X.; Zhang, H.; et al. Class A scavenger receptor deficiency exacerbates lung tumorigenesis by cultivating a procarcinogenic microenvironment in humans and mice. Am. J. Respir. Crit. Care Med. 2012, 186, 763-772.
90. Hagemann, T.; Wilson, J.; Burke, F.; Kulbe, H.; Li, N.F.; Plüddemann, A.; Charles, K.; Gordon, S.; Balkwill, F.R. Ovarian cancer cells polarize macrophages toward a tumor-associated phenotype. J. Immunol. 2006, 176, 5023-5032.
91. Bak, S.P.; Walters, J.J.; Takeya, M.; Conejo-Garcia, J.R.; Berwin, B.L. Scavenger receptor-A-targeted leukocyte depletion inhibits peritoneal ovarian tumor progression. Cancer Res. 2007, 67, 4783-4789.
92. Peter, S.; Bak, G.; Hart, K.; Berwin, B. Ovarian tumor-induced T cell suppression is alleviated by vascular leukocyte depletion. Transl. Oncol. 2009, 2, 291-299.
93. Komohara, Y.; Takemura, K.; Lei, X.F.; Sakashita, N.; Harada, M.; Suzuki, H.; Kodama, T.; Takeya, M. Delayed growth of EL4 lymphoma in SR-A-deficient mice is due to upregulation of nitric oxide and interferon-γ production by tumor-associated macrophages. Cancer Sci. 2009, 100, 2160-2166.
94. Neyen, C.; Plüddemann, A.; Mukhopadhyay, S.; Maniati, E.; Bossard, M.; Gordon, S.; Hagemann, T. Macrophage scavenger receptor a promotes tumor progression in murine models of ovarian and pancreatic cancer. J. Immunol. 2013, 190, 3798-3805.
95. Zhu, X.D.; Zhuang, Y.; Ben, J.J.; Qian, L.L.; Huang, H.P.; Bai, H.; Sha, J.H.; He, Z.G.; Chen, Q. Caveolae-Dependent endocytosis is required for class A macrophage scavenger receptor-mediated apoptosis in macrophages. J. Biol. Chem. 2011, 286, 8231-8239.
96. Ben, J.; Zhang, Y.; Zhou, R.; Zhang, H.; Zhu, X.; Li, X.; Zhang, H.; Li, N.; Zhou, X.; Bai, H.; et al. Major vault protein regulates class A scavenger receptor-mediated tumor necrosis factor-α synthesis and apoptosis in macrophages. J. Biol. Chem. 2013, 288, 20076-20084.
97. Nakamura, T.; Suzuki, H.; Wada, Y.; Kodama, T.; Doi, T. Fucoidan induces nitric oxide production via p38 mitogen-activated protein kinase and NF-κB-dependent signaling pathways through macrophage scavenger receptors. Biochem. Biophys. Res. Commun. 2006, 343, 286-294.
98. Berwin, B.; Hart, J.P.; Rice, S.; Gass, C.; Pizzo, S.V.; Post, S.R.; Nicchitta, C.V. Scavenger receptor-A mediates gp96/GRP94 and calreticulin internalization by antigen-presenting cells. EMBO J. 2003, 22, 6127-6136.
99. Herber, D.L.; Cao, W.; Nefedova, Y.; Novitskiy, S.V.; Nagaraj, S.; Tyurin, V.A.; Corzo, A.; Cho, H.I.; Celis, E.; Lennox, B.; et al. Lipid accumulation and dendritic cell dysfunction in cancer. Nat. Med. 2010, 16, 880-886.
100. Choi, J.I.; Raghavendran, H.R.; Sung, N.Y.; Kim, J.H.; Chun, B.S.; Ahn, D.H.; Choi, H.S.; Kang, K.W.; Lee, J.W. Effect of fucoidan on aspirin-induced stomach ulceration in rats. Chem. Biol. Interact. 2010, 183, 249-254.
101. Saito, A.; Yoneda, M.; Yokohama, S.; Okada, M.; Haneda, M.; Nakamura, K. Fucoidan prevents concanavalin A-induced liver injury through induction of endogenous IL-10 in mice. Hepatol. Res. 2006, 35, 190-198.
102. Cleveland, J.L.; Kastan, M.B. Cancer. A radical approach to treatment. Nature 2000, 407, 309-311.
103. Zhang, Z.; Teruya, K.; Yoshida, T.; Eto, H.; Shirahata, S. Fucoidan extract enhances the anti-cancer activity of chemotherapeutic agents in MDA-MB-231 and MCF-7 breast cancer cells. Mar. Drugs 2013, 11, 81-98.
104. Raghavendran, H.R.; Srinivasan, P.; Rekha, S. Immunomodulatory activity of fucoidan against aspirin-induced gastric mucosal damage in rats. Int. Immunopharmacol. 2011, 11, 157-163.
105. Cui, Y.Q.; Jia, Y.J.; Zhang, T.; Zhang, Q.B.; Wang, X.M. Fucoidan protects against lipopolysaccharide-induced rat neuronal damage and inhibits the production of proinflammatory mediators in primary microglia. CNS Neurosci. Ther. 2012, 18, 827-833.
106. Yanase, Y.; Hiragun, T.; Uchida, K.; Ishii, K.; Oomizu, S.; Suzuki, H.; Mihara, S.; Iwamoto, K.; Matsuo, H.; Onishi, N.; et al. Peritoneal injection of fucoidan suppresses the increase of plasma IgE induced by OVA-sensitization. Biochem. Biophys. Res. Commun. 2009, 387, 435-439.
107. 4-induced liver injury. Arch. Pharm. Res. 2008, 31, 622-627.
108. Luo, D.; Zhang, Q.; Wang, H.; Cui, Y.; Sun, Z.; Yang, J.; Zheng, Y.; Jia, J.; Yu, F.; Wang, X.; et al. Fucoidan protects against dopaminergic neuron death in vivo and in vitro. Eur. J. Pharmacol. 2009, 617, 33-40.
109. Balboa, E.M.; Conde, E.; Moure, A.; Falqué, E.; Domínguez, H. In vitro antioxidant properties of crude extracts and compounds from brown algae. Food Chem. 2013, 138, 1764-1785.
110. Hong, S.W.; Jung, K.H.; Lee, H.S.; Zheng, H.M; Choi, M.J.; Lee, C.; Hong, S.S. Suppression by fucoidan of liver fibrogenesis via the TGF-β/Smad pathway in protecting against oxidative stress. Biosci. Biotechnol. Biochem. 2011, 75, 833-840.
111. Hong, S.W.; Lee, H.S.; Jung, K.H.; Lee, H.; Hong, S.S. Protective effect of fucoidan against acetaminophen-induced liver injury. Arch. Pharm. Res. 2012, 35, 1099-1105.
112. Chen, J.; Wang, W.; Zhang, Q.; Li, F.; Lei, T.; Luo, D.; Zhou, H.; Yang, B. Low molecular weight fucoidan against renal ischemia-reperfusion injury via inhibition of the MAPK signaling pathway. PLoS One 2013, 8, e56224.
113. Lambert, J.D.; Elias, R.J. The antioxidant and pro-oxidant activities of green tea polyphenols: A role in cancer prevention. Arch. Biochem. Biophys. 2010, 501, 65-72.
114. Ye, J.; Li, Y.; Teruya, K.; Katakura, Y.; Ichikawa, A.; Eto, H.; Hosoi, M.; Hosoi, M.; Nishimoto, S.; Shirahata, S. Enzyme-Digested fucoidan extracts derived from seaweed Mozuku of Cladosiphon novae-caledoniae kylin inhibit invasion and angiogenesis of tumor cells. Cytotechnology 2005, 47, 117-126.