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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.
AuthorsRyogo Abu, Zedong Jiang, Mikinori Ueno, Shogo Isaka, Satoru Nakazono, Takasi Okimura, Kichul Cho, Kenichi Yamaguchi, Daekyung Kim, Tatsuya Oda
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 458 Issue 4 Pg. 727-32 (Mar 20 2015) ISSN: 1090-2104 [Electronic] United States
PMID25623538 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Inc. All rights reserved.
Chemical References
  • Adjuvants, Immunologic
  • Anticarcinogenic Agents
  • Polysaccharides
  • ascophyllin
  • Matrix Metalloproteinase 9
Topics
  • Adjuvants, Immunologic (chemistry, therapeutic use)
  • Animals
  • Anticarcinogenic Agents (chemistry, therapeutic use)
  • Ascophyllum (chemistry)
  • Cell Line, Tumor
  • Killer Cells, Natural (drug effects, immunology)
  • Lung (drug effects, immunology, metabolism, pathology)
  • Lung Neoplasms (immunology, metabolism, prevention & control, secondary)
  • MAP Kinase Signaling System (drug effects)
  • Male
  • Matrix Metalloproteinase 9 (metabolism)
  • Melanoma, Experimental (drug therapy, immunology, metabolism, pathology)
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Invasiveness (immunology, pathology, prevention & control)
  • Polysaccharides (chemistry, therapeutic use)
  • Spleen (cytology)

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