Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Chanez Manseur
ORCID logo ,
Hugo Groult
*,+ ORCID logo ,
Manon Porta
,
Pierre-Edouard Bodet
,
Nicolas Bridiau
ORCID logo ,
Rachida Mersni-Achour
,
Raphaëlle Petit
ORCID logo ,
Samir Ali-Moussa
,
Benjamin Musnier
,
Didier Le Cerf
ORCID logo ,
Tony Varacavoudin
,
Oualid Haddad
,
Angela Sutton
,
Jean-Marie Piot
,
Thierry Maugard
ORCID logo ,
Ingrid Fruitier-Arnaudin
*,+
+
These authors contributed equally to the work
Version 1 : Received: 20 March 2023 / Approved: 21 March 2023 / Online: 21 March 2023 (09:16:48 CET)

A peer-reviewed article of this Preprint also exists.

Manseur, C.; Groult, H.; Porta, M.; Bodet, P.-E.; Mersni-Achour, R.; Petit, R.; Ali-Moussa, S.; Musnier, B.; Le Cerf, D.; Varacavoudin, T.; Haddad, O.; Sutton, A.; Leal, C.E.Y.; Alencar-Filho, E.B.; Piot, J.-M.; Bridiau, N.; Maugard, T.; Fruitier-Arnaudin, I. 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. Mar. Drugs 2023, 21, 295. Manseur, C.; Groult, H.; Porta, M.; Bodet, P.-E.; Mersni-Achour, R.; Petit, R.; Ali-Moussa, S.; Musnier, B.; Le Cerf, D.; Varacavoudin, T.; Haddad, O.; Sutton, A.; Leal, C.E.Y.; Alencar-Filho, E.B.; Piot, J.-M.; Bridiau, N.; Maugard, T.; Fruitier-Arnaudin, I. 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. Mar. Drugs 2023, 21, 295.

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-CARs) is that they are in fact heterogeneous mixtures of different CARs families, and are named according to the thickening purpose of the product which does not reflect the real com-position. Consequently, this can limit their use in a clinical grade. To address this issue, six commercial λ-CARs were compared for which differences in their physiochemical properties were shown. Then, a H2O2-assissed radical depolymerization was applied to each commercial source and the 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 term of molar masses and DS, that ranged within previously reported values suitable for anti-tumor proper-ties. 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 indeed qualitative and semi-quantitative differences between the molecular species, especially in the proportion of the anti-HPSE λ-type, other CARs types and adjuvants, but 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.

Keywords

marine algae; lambda-carrageenan; oligosaccharides; heparanase; migration; anti-cancer agents

Subject

Chemistry and Materials Science, Analytical Chemistry

Copyright: 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.

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