Effects of Oral Administration of Fucoidan Extracted from Cladosiphon okamuranus on Tumor Growth and Survival Time in a Tumor-Bearing Mouse Model
Abstract
:1. Introduction
2. Results and Discussion
2.1. Effects of Oral Administration of Fucoidan in a Colon 26 Tumor-Bearing Mice Model
2.1.1. Effects of Oral Administration of Fucoidan on Tumor Growth
IMWF | Control | |
---|---|---|
Cell division cells (cells/field) | 93.3 ± 20.4 ** | 151.7 ± 14.5 |
TUNEL positive cells (cells/field) | 33.0 ± 12.8 | 24.3 ± 4.7 |
2.1.2. Effects of Oral Administration of Fucoidan on Survival Times
2.2. Effects of Oral Administration of Fucoidan on Splenic NK Cell Populations
2.3. Effects of Oral Administration of Fucoidan on Tumor Growing and Serum Cytokine in Myd-88 Knockout Mice
HMWF/Myd-88 group | control/Myd-88 group | |
---|---|---|
tumor weight (g) | 0.15 ± 0.06 | 0.18 ± 0.06 |
serum IL-2 (pg/mL) | 1.03 ± 0.01 | 1.00 ± 0.02 |
serum IL-10 (pg/mL) | 2.93 ± 1.23 | 2.12 ± 1.59 |
3. Experimental Section
3.1. Animals
3.2. Reagents
3.3. Preparation of the Tumor-Bearing Mouse Model
3.4. Tumor Growth Study
3.5. Histopathological Evaluation
3.6. Survival Time Study
3.7. Measurements of Splenic Natural Killer T Cells (NK Cells)
3.8. MyD-88 Knockout Mice Study
3.9. Statistical Analysis
4. Conclusions
References
- Li, B.; Lu, F.; Wei, X.; Zhao, R. Fucoidan: Structure and bioactivity. Molecules 2008, 13, 1671–1695. [Google Scholar] [CrossRef]
- Bilan, M.I.; Grachev, A.A.; Ustuzhanina, N.E.; Shashkov, A.S.; Nifantiev, N.E.; Usov, A.I. Structure of a fucoidan from the brown seaweed Fucus evanescens C. Ag. Carbohydr. Res. 2002, 337, 719–730. [Google Scholar] [CrossRef]
- Bilan, M.I.; Grachev, A.A.; Shashkov, A.S.; Nifantiev, N.E.; Usov, A.I. Structure of a fucoidan from the brown seaweed Fucus serratus L. Carbohydr. Res. 2006, 341, 238–245. [Google Scholar] [CrossRef]
- Hayashi, K.; Nakano, T.; Hashimoto, M.; Kanekiyo, K.; Hayashi, T. Defensive effects of a fucoidan from brown alga Undaria pinnatifida against herpes simplex virus infection. Int. Immunopharmacol. 2008, 8, 109–116. [Google Scholar] [CrossRef]
- Cumashi, A.; Ushakova, N.A.; Preobrazhenskaya, M.E.; D’Incecco, A.; Piccoli, A.; Totani, L.; Tinari, N.; Morozevich, G.E.; Berman, A.E.; Bilan, M.I.; et al. A comparative study of the anti-inflammatory, anticoagulant, antiangiogenic, and antiadhesive activities of nine different fucoidans from brown seaweeds. Glycobiology 2007, 17, 541–552. [Google Scholar]
- Croci, D.O.; Cumashi, A.; Ushakova, N.A.; Preobrazhenskaya, M.E.; Piccoli, A.; Totani, L.; Ustyuzhanina, N.E.; Bilan, M.I.; Usov, A.I.; Grachev, A.A.; et al. Fucans, but not fucomannoglucuronans, determine the biological activities of sulfated polysaccharides from Laminaria saccharina brown seaweed. PLoS One 2011, 6, e17283. [Google Scholar]
- Wang, J.; Zhang, Q.; Zhang, Z.; Li, Z. Antioxidant activity of sulfated polysaccharide fractions extracted from Laminaria japonica. Int. J. Biol. Macromol. 2008, 42, 127–132. [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]
- Choi, E.M.; Kim, A.J.; Kim, Y.O.; Hwang, J.K. Immunomodulating activity of arabinogalactan and fucoidan in vitro. J. Med. Food 2005, 8, 446–453. [Google Scholar] [CrossRef]
- Itoh, H.; Noda, H.; Amano, H.; Zhuaug, C.; Mizuno, T.; Ito, H. Antitumor activity and immunological properties of marine algal polysaccharides, especially fucoidan, prepared from Sargassum thunbergii of Phaeophycea. Anticancer Res. 1993, 13, 2045–2052. [Google Scholar]
- Zhuang, C.; Itoh, H.; Mizuno, T.; Ito, H. Antitumor active fucoidan from the brown seaweed, umitoranoo (Sargassum thunbergii). Biosci. Biotechnol. Biochem. 1995, 59, 563–567. [Google Scholar] [CrossRef]
- Koyanagi, S.; Tanigawa, N.; Nakagawa, H.; Soeda, S.; Shimeno, H. Oversulfation of fucoidan enhances its anti-angiogenic and antitumor activities. Biochem. Pharm. 2003, 65, 173–179. [Google Scholar]
- Riou, D.; Colliec-Jouault, S.; Pinczon du Sel, D.; Bosch, S.; Siavoshian, S.; Le Bert, V.; Tomasoni, C.; Sinquin, C.; Durand, P.; Roussakis, C. Antitumor and antiproliferative effects of a fucan extracted from Ascophyllum nodosum against a non-small-cell bronchopulmonary carcinoma line. Anticancer Res. 1996, 16, 1213–1218. [Google Scholar]
- Aisa, Y.; Miyakawa, Y.; Nakazato, T.; Shibata, H.; Saito, K.; Ikeda, Y.; Kizaki, M. Fucoidan induces apoptosis of human HS-sultan cells accompanied by activation of caspase-3 and down-regulation of ERK pathways. Am. J. Hematol. 2005, 78, 7–14. [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]
- Maruyama, H.; Takeuchi, 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]
- 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, 1754–1761. [Google Scholar] [CrossRef]
- Shimizu, J.; Wada-Funada, U.; Mano, H.; Matahira, Y.; Kawaguchi, M.; Wada, M. Proportion of murine cytotoxic T cells is increased by high molecular-weight fucoidan extracted from Okinawa mozuku (Cladosiphon okamuranus). J. Health Sci. 2004, 51, 394–397. [Google Scholar]
- Liu, J.M.; Bignon, J.; Haroum-Bouhedja, F.; Bittoun, P.; Vassy, J.; Fermandjian, S.; Wdzieczak-Bakala, J.; Boisson-Vidal, C. Inhibitory effect of fucoidan on the adhesion of adenocarcinoma cells to fibronectin. Anticancer Res. 2005, 25, 2129–2133. [Google Scholar]
- Kim, E.J.; Park, S.Y.; Lee, J.Y.; Park, J.H. Fucoidan present in brown algae induces apoptosis of human colon cancer. BMC Gastroenterol. 2010, 10, 86. [Google Scholar] [CrossRef]
- Salyers, A.A.; Vercellotti, J.R.; West, S.E.H.; Wilkins, T.D. Fermentation of mucin and plant polysaccharides by strains of bacteroides from the human colon. Appl. Environ. Microbiol. 1977, 33, 319–322. [Google Scholar]
- 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]
- 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]
- Caligiuri, M.A. Human natural killer cells. Blood 2008, 112, 461–469. [Google Scholar] [CrossRef]
- Stagg, J.; Smyth, M.J. NK cell-based cancer immunotherapy. Drug News Perspect. 2007, 20, 155–163. [Google Scholar] [CrossRef]
- Arancibia, S.A.; Beltrán, C.J.; Aguirre, I.M.; Silva, P.; Peralta, A.L.; Malinarich, F.; Hermoso, M.A. Toll-like receptors are key participants in innate immune response. Biol. Res. 2007, 40, 97–112. [Google Scholar]
- Akiea, S.; Takeda, K.; Kaisho, T. Toll-like receptors: critical proteins linking innate and acquired innunity. Nat. Immunol. 2001, 2, 675–680. [Google Scholar] [CrossRef]
- Akira, S. Toll-like receptors: Lessons from knockout mice. Biochem. Soc. Trans. 2000, 28, 551–556. [Google Scholar]
- Akira, S.; Uematsu, S.; Takeuchi, O. Pathogen recognition and innate immunity. Cell 2006, 24, 783–801. [Google Scholar]
- 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]
- Park, S.B.; Chun, K.R.; Kim, J.K.; Suk, K.; Jung, Y.M.; Lee, W.H. The differential effect of high and low molecular weight fucoidans on the severity of collagen-induced arthritis in mice. Phytother. Res. 2010, 24, 1384–1391. [Google Scholar] [CrossRef]
- Bilan, M.I.; Grachev, A.A.; Shashkov, A.S.; Kelly, M.; Sanderson, C.J.; Nifantiev, N.E.; Usov, A.I. Further studies on the composition and structure of a fucoidan preparation from the brown alga Saccharina latissima. Carbohydr. Res. 2010, 345, 2038–2047. [Google Scholar] [CrossRef]
- Teruya, T.; Takemoto, H.; Konishi, T.; Tako, M. Structural characteristics and in vitro macrophage activation of acetyl fucoidan from Cladosiphon okamuranus. Glycoconj. J. 2009, 29, 1019–1028. [Google Scholar]
- Sato, K.; Saimoto, H.; Morimoto, M.; Shigemasa, Y. Depolymerization of chitin and chitosan under the hydrothermal conditions. Sen’i Gakkaishi 2003, 59, 104–109. [Google Scholar] [CrossRef]
- Samples Availability: Available from the authors.
© 2012 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
Azuma, K.; Ishihara, T.; Nakamoto, H.; Amaha, T.; Osaki, T.; Tsuka, T.; Imagawa, T.; Minami, S.; Takashima, O.; Ifuku, S.; 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. https://doi.org/10.3390/md10102337
Azuma K, Ishihara T, Nakamoto H, Amaha T, Osaki T, Tsuka T, Imagawa T, Minami S, Takashima O, Ifuku S, et al. Effects of Oral Administration of Fucoidan Extracted from Cladosiphon okamuranus on Tumor Growth and Survival Time in a Tumor-Bearing Mouse Model. Marine Drugs. 2012; 10(10):2337-2348. https://doi.org/10.3390/md10102337
Chicago/Turabian StyleAzuma, Kazuo, Toshitsugu Ishihara, Hiroyuki Nakamoto, Takao Amaha, Tomohiro Osaki, Takeshi Tsuka, Tomohiro Imagawa, Saburo Minami, Osamu Takashima, Shinsuke Ifuku, and et al. 2012. "Effects of Oral Administration of Fucoidan Extracted from Cladosiphon okamuranus on Tumor Growth and Survival Time in a Tumor-Bearing Mouse Model" Marine Drugs 10, no. 10: 2337-2348. https://doi.org/10.3390/md10102337