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Mar. Drugs 2019, 17(3), 140; https://doi.org/10.3390/md17030140

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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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)
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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 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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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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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