期刊
MARINE DRUGS
卷 17, 期 3, 页码 -出版社
MDPI
DOI: 10.3390/md17030140
关键词
lambda-carrageenan; heparanase; anticoagulant; depolymerisation; cell migration
资金
- Ligue Contre le Cancer (Comite CD17 Charente Maritime and CSIRGO)
- Region Nouvelle Aquitaine (Nanovect Project)
In tumor development, the degradation of heparan sulfate (HS) by heparanase (HPSE) is associated with cell-surface and extracellular matrix remodeling as well as the release of HS-bound signaling molecules, allowing cancer cell migration, invasion and angiogenesis. Because of their structural similarity with HS, sulfated polysaccharides are considered a promising source of molecules to control these activities. In this study, we used a depolymerisation method for producing -carrageenan oligosaccharides (-CO), with progressive desulfation over time. These were then used to investigate the influence of polymeric chain length and degree of sulfation (DS) on their anti-HPSE activity. The effects of these two features on -CO anticoagulant properties were also investigated to eliminate a potential limitation on the use of a candidate -CO as a chemotherapeutic agent. HPSE inhibition was mainly related to the DS of -CO, however this correlation was not complete. On the other hand, both chain length and DS modulated -CO activity for factor Xa and thrombin IIa inhibition, two enzymes that are involved in the coagulation cascade, and different mechanisms of inhibition were observed. A -carrageenan oligosaccharide of 5.9 KDa was identified as a suitable anticancer candidate because it displayed one of the lowest anticoagulant properties among the -CO produced, while showing a remarkable inhibitory effect on MDA-MB-231 breast cancer cell migration.
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