λ-Carrageenan Oligosaccharides of Distinct Anti-Heparanase and Anticoagulant Activities Inhibit MDA-MB-231 Breast Cancer Cell Migration

Marine Drugs
Hugo GroultIngrid Fruitier-Arnaudin

Abstract

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 λ-carrageenan oligosaccharides (λ-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 λ-CO anticoagulant properties were also investigated to eliminate a potential limitation on the use of a candidate λ-CO as a chemotherapeutic agent. HPSE inhibition was mainly related to the DS of λ-CO, however this correlation was not complete. On the other hand, both chain length and DS modulated λ-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 λ-carrageenan oligosaccharide of 5.9 KDa was ide...Continue Reading

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Citations

Dec 19, 2020·Marine Drugs·Sergey A Dyshlovoy, Friedemann Honecker
Feb 6, 2021·Carbohydrate Polymers·Jia-Li JiangJing-Wei Shao
Mar 31, 2020·European Journal of Medicinal Chemistry·Kaishuo FuWen Zhou
Aug 6, 2021·Scientific Reports·Mariana Paranhos StellingMauro Sérgio Gonçalves Pavão

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Methods Mentioned

BETA
acetylation
FRET
Size
size exclusion chromatography
fluorescence

Software Mentioned

HP Chemstation
SigmaPlot

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