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Open AccessArticle

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

Equipe BCBS (Biotechnologies et Chimie des Bioressources pour la Santé), Université de La Rochelle, UMR CNRS 7266 LIENSs, 17000 La Rochelle, France
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Mar. Drugs 2019, 17(3), 140; https://doi.org/10.3390/md17030140
Received: 8 January 2019 / Revised: 15 February 2019 / Accepted: 22 February 2019 / Published: 27 February 2019
(This article belongs to the Collection Marine Compounds and Cancer)
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 identified as a suitable anticancer candidate because it displayed one of the lowest anticoagulant properties among the λ-CO produced, while showing a remarkable inhibitory effect on MDA-MB-231 breast cancer cell migration. View Full-Text
Keywords: λ-carrageenan; heparanase; anticoagulant; depolymerisation; cell migration λ-carrageenan; heparanase; anticoagulant; depolymerisation; cell migration
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Groult, H.; Cousin, R.; Chot-Plassot, C.; Maura, M.; Bridiau, N.; Piot, J.-M.; Maugard, T.; Fruitier-Arnaudin, I. λ-Carrageenan Oligosaccharides of Distinct Anti-Heparanase and Anticoagulant Activities Inhibit MDA-MB-231 Breast Cancer Cell Migration. Mar. Drugs 2019, 17, 140.

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