title: Anti-heparanase activity of ultra-low-molecular-weight heparin produced by physicochemical depolymerization.
abstract: Heparanase is an endo-β-D-glucuronidase that plays an important role in cancer progression, in particular during tumor angiogenesis and metastasis. Inhibiting this enzyme is considered as one of the most promising approaches in cancer therapy. Heparin is a complex glycoaminoglycan known as a strong inhibitor of heparanase. It is primarily used in clinical practice for its anticoagulant activities, which may not be compatible with its use as anti-angiogenic agent. In this study, we described the production of ultra-low-molecular-weight heparins (ULMWH) by a physicochemical method that consists in a hydrogen peroxide-catalyzed radical hydrolysis assisted by ultrasonic waves. We assessed the structural characteristics, anticoagulant and anti-heparanase activities of the obtained heparin derivatives and compared them with three commercial low-molecular-weight heparins (LMWH), glycol-split non-anticoagulant heparins and heparins produced by enzymatic methods. ULMWH generated by the physicochemical method were characterized by high anti-heparanase and moderate anticoagulant activities. These heparin derivatives might be potential candidates for cancer therapy when a compromise is needed between anti-heparanase and anticoagulant activities.
authors.affiliation: Université de La Rochelle, UMR CNRS 7266, LIENSS, Equipe Approches Moléculaires Environnement-Santé, Département de Biotechnologies, Avenue Michel Crépeau, 17042 La Rochelle, France.
authors.forename: Oussama
authors.initials: O
authors.lastname: Achour
authors.affiliation: Université de La Rochelle, UMR CNRS 7266, LIENSS, Equipe Approches Moléculaires Environnement-Santé, Département de Biotechnologies, Avenue Michel Crépeau, 17042 La Rochelle, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Poupard
authors.affiliation: Université de La Rochelle, UMR CNRS 7266, LIENSS, Equipe Approches Moléculaires Environnement-Santé, Département de Biotechnologies, Avenue Michel Crépeau, 17042 La Rochelle, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bridiau
authors.affiliation: Université de La Rochelle, UMR CNRS 7266, LIENSS, Equipe Approches Moléculaires Environnement-Santé, Département de Biotechnologies, Avenue Michel Crépeau, 17042 La Rochelle, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bordenave Juchereau
authors.affiliation: Université de La Rochelle, UMR CNRS 7266, LIENSS, Equipe Approches Moléculaires Environnement-Santé, Département de Biotechnologies, Avenue Michel Crépeau, 17042 La Rochelle, France.
authors.forename: Fredéric
authors.initials: F
authors.lastname: Sannier
authors.affiliation: Université de La Rochelle, UMR CNRS 7266, LIENSS, Equipe Approches Moléculaires Environnement-Santé, Département de Biotechnologies, Avenue Michel Crépeau, 17042 La Rochelle, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Piot
authors.affiliation: Université de La Rochelle, UMR CNRS 7266, LIENSS, Equipe Approches Moléculaires Environnement-Santé, Département de Biotechnologies, Avenue Michel Crépeau, 17042 La Rochelle, France.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Fruitier Arnaudin
authors.affiliation: Université de La Rochelle, UMR CNRS 7266, LIENSS, Equipe Approches Moléculaires Environnement-Santé, Département de Biotechnologies, Avenue Michel Crépeau, 17042 La Rochelle, France. Electronic address: tmaugard@univ-lr.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Maugard
mesh_terms: D000925:Anticoagulants / Q000737:chemistry*; D002384:Catalysis; D005966:Glucuronidase / Q000737:chemistry*; D006493:Heparin / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry; D006868:Hydrolysis; D008970:Molecular Weight; D000069453:Ultrasonic Waves; D000099175:Heparanase
chemical_list: D000925:Anticoagulants; D005966:Glucuronidase; D006493:Heparin; D006861:Hydrogen Peroxide; D000099175:Heparanase
keywords: Anti-angiogenesis; Glycol-split; Heparanase; Heparin; Heparinase I-catalyzed β-elimination; Ultrasonic-assisted radical hydrolysis