title: Anti-metastatic effects of the sulfated polysaccharide ascophyllan isolated from Ascophyllum nodosum on B16 melanoma.
abstract: We previously found that ascophyllan, a sulfated polysaccharide isolated from brown seaweed Ascophyllum nodosum, exhibited antitumor activity in sarcoma-180 tumor-bearing mice. In this study, we found that ascophyllan inhibited the migration and adhesion of B16 melanoma cells by reducing the expression of N-cadherin and enhancing the expression of E-cadherin in a concentration-dependent manner. Transwell invasion assay revealed that ascophyllan suppressed the invasion ability of B16 cells. It also inhibited the expression of matrix metalloprotease-9 (MMP-9) mRNA and the secretion of MMP-9 protein in B16 cells, a process that may involve the extracellular signal-regulated kinase (ERK) signaling pathway. Furthermore, ascophyllan administered intraperitoneally at 25 mg/kg showed anti-metastatic activity in a mouse model of metastasis induced by intravenous injection of B16 cells, and the number of lung surface metastatic nodules in ascophyllan-treated mice was significantly reduced compared to that in the untreated control mice. Since splenic natural killer cell activity enhanced in the mice injected with ascophyllan intraperitoneally, we suggest that ascophyllan may exhibit in vivo anti-metastatic activity on B16 melanoma cells through activation of the host immune system in addition to a direct action on cancer cells.
authors.affiliation: Graduate School of Fisheries Science and Environmental Studies, Nagasaki University, Nagasaki 852-8521, Japan.
authors.forename: Ryogo
authors.initials: R
authors.lastname: Abu
authors.affiliation: College of Food and Biological Engineering, Jimei University, Xiamen, Fujian Province 361021, China.
authors.forename: Zedong
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Graduate School of Fisheries Science and Environmental Studies, Nagasaki University, Nagasaki 852-8521, Japan.
authors.forename: Mikinori
authors.initials: M
authors.lastname: Ueno
authors.affiliation: Graduate School of Fisheries Science and Environmental Studies, Nagasaki University, Nagasaki 852-8521, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Isaka
authors.affiliation: Graduate School of Fisheries Science and Environmental Studies, Nagasaki University, Nagasaki 852-8521, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Nakazono
authors.affiliation: Research and Development Division, Hayashikane Sangyo Co., Ltd., Shimonoseki, Yamaguchi 750-8608, Japan.
authors.forename: Takasi
authors.initials: T
authors.lastname: Okimura
authors.affiliation: Jeju Center, Korea Basic Science Institute (KBSI), Jeju 690-756, Republic of Korea; Korea University of Science & Technology, Daejeon 305-350, Republic of Korea.
authors.forename: Kichul
authors.initials: K
authors.lastname: Cho
authors.affiliation: Graduate School of Fisheries Science and Environmental Studies, Nagasaki University, Nagasaki 852-8521, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Jeju Center, Korea Basic Science Institute (KBSI), Jeju 690-756, Republic of Korea; Korea University of Science & Technology, Daejeon 305-350, Republic of Korea. Electronic address: dkim@kbsi.re.kr.
authors.forename: Daekyung
authors.initials: D
authors.lastname: Kim
authors.affiliation: Graduate School of Fisheries Science and Environmental Studies, Nagasaki University, Nagasaki 852-8521, Japan. Electronic address: t-oda@nagasaki-u.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Oda
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000627:therapeutic use*; D044646:Ascophyllum / Q000737:chemistry*; D045744:Cell Line, Tumor; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control* / Q000556:secondary*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D011134:Polysaccharides / Q000737:chemistry / Q000627:therapeutic use*; D013154:Spleen / Q000166:cytology
chemical_list: D000276:Adjuvants, Immunologic; D016588:Anticarcinogenic Agents; D011134:Polysaccharides; C058519:ascophyllin; D020780:Matrix Metalloproteinase 9
keywords: Ascophyllan; Ascophyllum nodosum; B16 melanoma; Melanoma metastasis; Sulfated polysaccharide