Fucoidan as a Marine Anticancer Agent in Preclinical Development
Abstract
:1. Introduction
2. Cancer Cell Apoptosis in Vitro
Fucoidan | Route/Dose | Tumor Type | Action Mechanism | References |
---|---|---|---|---|
Cladosiphon okamuranus | p.o. 5 g/kg | 26 colon cancer cells | Natural killer (NK) cell-mediated | [11] |
Fucus vesiculosus (Sigma, St. Louis, MO, USA) | i.p. 5 mg/kg | 4T1 breast cancer cells | Inhibition of angiogenesis and induction of apoptosis | [24,25] |
Fucus evanescence | 10 mg/kg | Lewis lung carcinoma cells | Unknown | [27] |
From Ze Lang Nanjing Med. Tech Co. | i.p. 200 mg/kg | Bel-7402 hepatocellular carcinoma in nude mice | Inhibition of proliferation | [28] |
Fucus vesiculosus (Sigma, St. Louis, MO, USA) | Foot-pad injection 0.25 mg/mice | 4T1-xenograft mice | Prevention of metastasis | [29] |
Sargassum plagiophyllum | p.o. 75 mg/kg | Diethylnitrosamine-induced hepatocellular carcinoma | Inhibition of carcinogen metabolism | [30] |
Cladosiphon okamuranus Tokida | p.o. 100 mg/kg | Sarcoma 180 (S-180)-xenograft | Delayed tumor growth by nitric oxide produced by macrophages | [31] |
Undaria pinnatifida | Diet containing 1% Mekabu (34 mg/day) | A20 leukemia cells | Cytolytic activity by NK cell activation | [32] |
Fucus vesiculosus (Sigma, St. Louis, MO, USA) | i.v. 5 mg/kg | Lewis lung carcinoma cells B16 melanoma cells | Antiangiogenic effect | [33] |
Ascophyllum nodosum | 1 mg/mice | MOPC-315 plasma cell tumor | Prevention of angiogenesis in tumor tissues | [34] |
3. In Vivo Anticancer Effects
4. In Vivo Anticancer Immune Responses
5. Antiangiogenic Effects of Fucoidan in Vivo
6. Mobilization of Hematopoietic Progenitor Cells
Test | Route | Dose | Possible in vivo effects | References |
---|---|---|---|---|
Human | p.o. | 330 mg | Mobilization of leukocytes | [12] |
Human | p.o. | 100 mg | Immune modulation | [15] |
Rabbit | i.v. | 10 mg/kg | Decreased influx of leukocytes into cerebrospinal fluid in meningitis | [58] |
Mice | i.v. i.p. | 50 mg/kg 50 mg/kg | Mobilization of hematopoietic progenitor stem cells (HPCs) | [61,62,63] |
Rat | i.p. | 25 mg/kg | Inhibition of extravasation of macrophages and CD4+ T cells to myocardium | [64] |
Mice | p.o. | 200 mg/kg | Th1 switch in Leishmania infection | [65] |
Mice | i.p. | 50 mg/kg | Improvement of pulmonary inflammation | [66] |
Rat | i.p. | 50 mg/kg | Inhibition of leukocyte infiltration in ischemic lesion | [67] |
Mice | i.v. | 10 mg/kg | Inhibition of infiltration of γδ T cells in pleural cavity | [68] |
Mice | p.o. | 0.05% (w/w) in mouse chow | Improvement of chronic colitis | [69] |
Mice | i.v. | 25 mg/kg | Inhibition of leukocyte rolling | [70] |
Rat | p.o. | 100 mg/kg | Decreased infiltration of neutrophils in myocardial infarct size | [71] |
Cat | i.v. | 25 mg/kg | Inhibition of leukocyte rolling | [72] |
7. Role of Scavenger Receptor Type A in the Action of Fucoidan
8. In Vivo Cytokine Production by Fucoidan in Other Diseases
9. In Vivo Antioxidant and Prooxidant Effects of Fucoidan
Cytokines | In Vivo Changes | References |
---|---|---|
CXCL12 | Increase in plasma | [37,51,61,63,80] |
Increase in myocardial ischemic tissue | [46] | |
IFN-γ | Increase in splenic T cells/A20 lymphoma | [32] |
Increase in splenic T cells/P-388 | [40] | |
Increase of secretion in plasma by aspirin | [100] | |
Inhibition of increase in gastric ulcer lesion | [104] | |
TNF-α | Inhibition of increase in acute bacterial meningitis | [58] |
Inhibition of expression in ischemic lesion | [67] | |
Inhibition of increase in ischemia-reperfusion injury | [71] | |
Inhibition of increase in gastric ulcer lesion | [104] | |
Inhibition of lipopolysaccharide-induced increase in brain | [105] | |
IL-1 | Inhibition of increase in acute bacterial meningitis | [58] |
IL-4 | Decrease in bronchoalveolar lavage fluid | [66] |
Decrease in ovalbumin-sensitized spleen cells | [106] | |
IL-5 | Inhibition of increase in pleural cavity of allergic pleurisy | [68] |
IL-6 | Decrease in plasma | [15] |
Inhibition of increase in colonic lamina propria of colitis | [69] | |
Inhibition of increase in ischemia-reperfusion injury | [71] | |
IL-8 | Increase in plasma | [63] |
Inhibition of lipopolysaccharide-induced increase in brain | [67,105] | |
IL-10 | Increase in plasma level in liver injury | [101] |
Inhibition of decrease in ischemia-reperfusion injury | [71] | |
IL-12 | Increase in splenic T cells/A20 lymphoma | [32] |
Increase in Leishmania infection | [65] | |
Inhibition of increase in gastric ulcer lesion | [104] | |
MCP-1 | Increase in plasma | [63] |
VEGF | Reduction of mRNA expression in tumor tissues | [24] |
Increase in myocardial ischemic tissue | [46] | |
FGF-2 | Potentiation of activity | [37] |
Test | Route | Dose | Possible in vivo effects | References |
---|---|---|---|---|
Mice | i.p. | 25 mg/kg 15 mg/kg | Prevention of MPTP-induced neurotoxicity Prevention of lipopolysaccharide-induced neurotoxicity | [108] [105] |
Mice | i.p. | 25 mg/kg | Neuroprotection via antioxidant activity | [108] |
Mice | i.p. | 100 mg/kg | Prevention of ischemia-reperfusion injury | [112] |
Rat | p.o. i.p. | 100 mg/kg | Suppression of liver fibrogenesis and drug-induced liver injury | [110,111] |
10. Conclusions
Acknowledgments
Conflicts of Interest
References
- Pomin, V.H.; Mourão, P.A. Structure, biology, evolution, and medical importance of sulfated fucans and galactans. Glycobiology 2008, 18, 1016–1027. [Google Scholar] [CrossRef]
- Fitton, J.H. Therapies from fucoidan; multifunctional marine polymers. Mar. Drugs 2011, 9, 1731–1760. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- Kim, M.H.; Joo, H.G. Immunostimulatory effects of fucoidan on bone marrow-derived dendritic cells. Immunol. Lett. 2008, 115, 138–143. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- Irhimeh, M.R.; Fitton, J.H.; Lowenthal, R.M. Fucoidan ingestion increases the expression of CXCR4 on human CD34+ cells. Exp. Hematol. 2007, 35, 989–994. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- Li, N.; Zhang, Q.; Song, J. Toxicological evaluation of fucoidan extracted from Laminaria japonica in Wistar rats. Food Chem. Toxicol. 2005, 43, 421–426. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- Lippitz, B.E. Cytokine patterns in patients with cancer: A systematic review. Lancet Oncol. 2013, 14, e218–e228. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- Palucka, K.; Banchereau, J. Cancer immunotherapy via dendritic cells. Nat. Rev. Cancer 2012, 12, 265–277. [Google Scholar] [CrossRef]
- Tejpar, S.; Prenen, H.; Mazzone, M. Overcoming resistance to antiangiogenic therapies. Oncologist 2012, 17, 1039–1050. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- Wang, Y.Q.; Miao, Z.H. Marine-derived angiogenesis inhibitors for cancer therapy. Mar. Drugs 2013, 11, 903–933. [Google Scholar] [CrossRef]
- Arfors, K.E.; Ley, K. Sulfated polysaccharides in inflammation. J. Lab. Clin. Med. 1993, 121, 201–202. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- Nervi, B.; Link, D.C.; DiPersio, J.F. Cytokines and hematopoietic stem cell mobilization. J. Cell. Biochem. 2006, 99, 690–705. [Google Scholar] [CrossRef]
- Zlotnik, A. New insights on the role of CXCR4 in cancer metastasis. J. Pathol. 2008, 215, 211–213. [Google Scholar] [CrossRef]
- Furusato, B.; Mohamed, A.; Uhlén, M.; Rhim, J.S. CXCR4 and cancer. Pathol. Int. 2010, 60, 497–505. [Google Scholar]
- Teicher, B.A.; Fricker, S.P. CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clin. Cancer Res. 2010, 16, 2927–2931. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- Brown, M.S.; Goldstein, J.L. Lipoprotein metabolism in the macrophage: Implications for cholesterol deposition in atherosclerosis. Annu. Rev. Biochem. 1983, 52, 223–261. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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-γproduction by tumor-associated macrophages. Cancer Sci. 2009, 100, 2160–2166. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- Cleveland, J.L.; Kastan, M.B. Cancer. A radical approach to treatment. Nature 2000, 407, 309–311. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- Kang, K.S.; Kim, I.D.; Kwon, R.H.; Lee, J.Y.; Kang, J.S.; Ha, B.J. The effects of fucoidan extracts on CCl4-induced liver injury. Arch. Pharm. Res. 2008, 31, 622–627. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar]
- 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. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
© 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
Share and Cite
Kwak, J.-Y. Fucoidan as a Marine Anticancer Agent in Preclinical Development. Mar. Drugs 2014, 12, 851-870. https://doi.org/10.3390/md12020851
Kwak J-Y. Fucoidan as a Marine Anticancer Agent in Preclinical Development. Marine Drugs. 2014; 12(2):851-870. https://doi.org/10.3390/md12020851
Chicago/Turabian StyleKwak, Jong-Young. 2014. "Fucoidan as a Marine Anticancer Agent in Preclinical Development" Marine Drugs 12, no. 2: 851-870. https://doi.org/10.3390/md12020851