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

• Published in: Marine drugs 2023-05, Vol.21 (5), p.295
• Main Authors: Manseur, Chanez, Groult, Hugo, Porta, Manon, Bodet, Pierre-Edouard, Mersni-Achour, Rachida, Petit, Raphaëlle, Ali-Moussa, Samir, Musnier, Benjamin, Le Cerf, Didier, Varacavoudin, Tony, Haddad, Oualid, Sutton, Angela, Leal, Cíntia Emi Yanaguibashi, Alencar-Filho, Edilson Beserra, Piot, Jean-Marie, Bridiau, Nicolas, Maugard, Thierry, Fruitier-Arnaudin, Ingrid
• Format: Article
• Language: English
• Subjects: Adjuvants; Algae; anticancer agents; Anticancer properties; Anticoagulants; Antimitotic agents; Antineoplastic agents; Antitumour agents; Cancer; Carrageenan; Carrageenan - chemistry; Carrageenan - pharmacology; Carrageenans; Carrageenin; Cell cycle; Cell migration; Chemical properties; Chemical Sciences; Composition; Depolymerization; Enzyme inhibitors; Formulations; Health aspects; Heparan sulfate; heparanase; Humans; Hydrogen peroxide; Hydrogen Peroxide - pharmacology; lambda-carrageenan; Life Sciences; Manganese; marine algae; Marine resources; migration; Mixtures; Neoplasms; NMR; Nuclear magnetic resonance; Oligosaccharides; Oligosaccharides - chemistry; Oligosaccharides - pharmacology; Pharmaceutical research; Pharmaceuticals; Physiochemistry; Production processes; Qualitative analysis; Saccharides; Sulfation; Therapeutic applications; Viscosity
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md21050295

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 H O -assisted depolymerization was applied to each commercial source, and number- and weight-averaged molar masses (M and M ) 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 H O -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.