A Screening Approach to Assess the Impact of Various Commercial Sources of Crude Marine λ-Carrageenan on the Production of Oligosaccharides with Anti-heparanase and Anti-migratory Activities
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Published:2023-05-11
Issue:5
Volume:21
Page:295
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ISSN:1660-3397
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Container-title:Marine Drugs
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language:en
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Short-container-title:Marine Drugs
Author:
Manseur Chanez1ORCID, Groult Hugo1ORCID, Porta Manon1, Bodet Pierre-Edouard1ORCID, Mersni-Achour Rachida1, Petit Raphaëlle1ORCID, Ali-Moussa Samir1, Musnier Benjamin1, Le Cerf Didier2ORCID, Varacavoudin Tony2, Haddad Oualid3, Sutton Angela3, Leal Cíntia Emi Yanaguibashi4, Alencar-Filho Edilson Beserra4ORCID, Piot Jean-Marie1, Bridiau Nicolas1ORCID, Maugard Thierry1ORCID, Fruitier-Arnaudin Ingrid1
Affiliation:
1. UMR CNRS 7266, LIENSs Laboratory, La Rochelle University, 17000 La Rochelle, France 2. Sciences & Technic Faculty, Univ Rouen Normandie, INSA Rouen Normandie, CNRS, PBS UMR 6270, 76000 Rouen, France 3. Inserm U1148, Laboratory for Vascular Translational Science, UFR SMBH, Université Paris 13, Sorbonne Paris Cité, Groupe Biothérapies et Glycoconjugués, 93000 Bobigny, France 4. College of Pharmaceutical Sciences, Federal University of Vale do São Francisco (UNIVASF), Petrolina 56304-205, PE, Brazil
Abstract
Oligosaccharides derived from λ-carrageenan (λ-COs) are gaining interest in the cancer field. They have been recently reported to regulate heparanase (HPSE) activity, a protumor enzyme involved in cancer cell migration and invasion, making them very promising molecules for new therapeutic applications. However, one of the specific features of commercial λ-carrageenan (λ-CAR) is that they are heterogeneous mixtures of different CAR families, and are named according to the thickening-purpose final-product viscosity which does not reflect the real composition. Consequently, this can limit their use in a clinical applications. To address this issue, six commercial λ-CARs were compared and differences in their physiochemical properties were analyzed and shown. Then, a H2O2-assisted depolymerization was applied to each commercial source, and number- and weight-averaged molar masses (Mn and Mw) and sulfation degree (DS) of the λ-COs produced over time were determined. By adjusting the depolymerization time for each product, almost comparable λ-CO formulations could be obtained in terms of molar masses and DS, which ranged within previously reported values suitable for antitumor properties. However, when the anti-HPSE activity of these new λ-COs was screened, small changes that could not be attributed only to their small length or DS changes between them were found, suggesting a role of other features, such as differences in the initial mixture composition. Further structural MS and NMR analysis revealed qualitative and semi-quantitative differences between the molecular species, especially in the proportion of the anti-HPSE λ-type, other CARs types and adjuvants, and it also showed that H2O2-based hydrolysis induced sugar degradation. Finally, when the effects of λ-COs were assessed in an in vitro migration cell-based model, they seemed more related to the proportion of other CAR types in the formulation than to their λ-type-dependent anti-HPSE activity.
Funder
Ligue Contre le Cancer Region Nouvelle Aquitaine ANR
Subject
Drug Discovery,Pharmacology, Toxicology and Pharmaceutics (miscellaneous),Pharmaceutical Science
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