title: Interference with the CXCL12/CXCR4 axis as potential antitumor strategy: superiority of a sulfated galactofucan from the brown alga Saccharina latissima and fucoidan over heparins.
abstract: The present study demonstrates that fucose-containing sulfated polysaccharides (FCSP) from brown algae interfere with the CXCL12/CXCR4 axis in human Burkitt's lymphoma cells by binding CXCL12 and thereby blocking both CXCL12-induced CXCR4 receptor activation and downstream effects like migration and secretion of matrix metalloproteinase-9. This mode of action is currently considered as promising strategy for tumor therapy and may contribute to the known in vivo antitumor, antimetastatic and antiangiogenic activity of FCSP. In terms of the inhibition of the CXCR4 activation, FCSP from Saccharina latissima (S.l.-FCSP) proved to be more active than a commercial "Fucoidan" from Fucus vesiculosus, and both FCSP were superior to heparins by more than one order of magnitude. Fractionation of S.l.-FCSP revealed that its main fraction is composed of a homogeneous, higher sulfated galactofucan (S.l.-SGF) which consistently exhibited stronger activities and can therefore be considered as the active ingredient of S.l.-FCSP. By subjecting Fucoidan to the same fractionation procedure, the inhibitory activity of the obtained purified Fucoidan on the CXCL12/CXCR4 axis tended to be weaker and its antioxidant and antiproliferative effects were lost. This was probably due to the separation of contaminants including phenolic compounds, whose content additionally showed marked batch-to-batch variability. Regarding the need of standardized, well-characterized FCSP preparations for any potential medical application, our results indicate that S.l.-SGF is a promising candidate for further investigations and that S. latissima may be a more appropriate source of FCSP than F. vesiculosus or other algae species with high contents of co-extractable compounds.
authors: Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Gutenbergstrasse 76, 24118 Kiel, Germany.
authors: Tino
authors: T
authors: Schneider
authors: Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Gutenbergstrasse 76, 24118 Kiel, Germany.
authors: Karina
authors: K
authors: Ehrig
authors: Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Gutenbergstrasse 76, 24118 Kiel, Germany.
authors: Inga
authors: I
authors: Liewert
authors: Pharmaceutical Institute, Christian-Albrechts-University of Kiel, Gutenbergstrasse 76, 24118 Kiel, Germany salban@pharmazie.uni-kiel.de.
authors: Susanne
authors: S
authors: Alban
mesh_terms: D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000037:antagonists & inhibitors; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016166:Free Radical Scavengers / Q000302:isolation & purification / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D000459:Phaeophyceae / Q000737:chemistry*; D010851:Picrates / Q000037:antagonists & inhibitors; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D011485:Protein Binding; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D016166:Free Radical Scavengers; D010851:Picrates; D011134:Polysaccharides; D019718:Receptors, CXCR4; D006493:Heparin; C007789:fucoidan; C004931:1,1-diphenyl-2-picrylhydrazyl; D020780:Matrix Metalloproteinase 9
keywords: CXCL12/CXCR4 axis; Saccharina latissima; antitumor; fucoidan; heparin