title: Apo-neocarzinostatin: a protein carrier for Cu(II) glycocomplexes and Cu(II) into U937 and HT29 cell lines.
abstract: In the field of pharmaceuticals there is an increasing need for new delivery systems to overcome the issues of solubility, penetration, toxicity and drug resistance. One of the possible strategies is to use biocarriers such as proteins to encourage the cell-penetration of drugs. In this paper, the use of the apo-protein neocarzinostatin (apo-NCS) as a carrier-protein for two Cu(II) glycocomplexes, previously characterized, and Cu(II) ions was investigated. Its interaction with the metallic compounds was analyzed using microcalorimetry. The dissociation constants were shown to be in the micromolar range. The Cu(II) glycocomplexes, in absence of apo-NCS, were found to be cytotoxic in the U937 and HT29 cell lines whereas the corresponding glycoligands showed no toxicity. The leukemic cell line (U937) seems to be more sensitive to glycocomplexes than the colon cancer cell line (HT29). Interestingly, apo-NCS was shown to increase systematically the antiproliferative activity by a factor of 2 and 3 for Cu(II) glycocomplexes and Cu(II) respectively. The antiproliferative activity detected was not related to proteasome inhibition. This result stresses the importance of new molecular tools for the delivery of Cu(II) to tumor cells using non-covalent association with carriers proteins.
authors.affiliation: Institut de Chimie Moléculaire et des Matériaux d'Orsay, Equipe de Chimie Bioorganique et Bioinorganique, Univ. Paris-Sud 11, F-91405 Orsay Cedex, France.
authors.forename: Ludivine
authors.initials: L
authors.lastname: Garcia
authors.affiliation: Dipartimento di Bioscienze, Università degli Studi di Parma, Parco Area delle Scienze 11A, 43124 Parma, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Franzoni
authors.affiliation: Dipartimento di Bioscienze, Università degli Studi di Parma, Parco Area delle Scienze 11A, 43124 Parma, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mussi
authors.affiliation: Institut de Biochimie et Biophysique Moléculaire et Cellulaire (UMR8619), Univ. Paris-Sud 11, F-91405 Orsay Cedex, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Aumont-Niçaise
authors.affiliation: Ecole Normale Supérieure, Département Chimie, 24 rue Lhomond, F-75005 Paris France; Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 Place Jussieu, 75005 Paris, France; Laboratoire des BioMolécules, UMR7203, CNRS, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Bertrand
authors.affiliation: Institut de Biochimie et Biophysique Moléculaire et Cellulaire (UMR8619), Univ. Paris-Sud 11, F-91405 Orsay Cedex, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Desmadril
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Parma, Parco Area delle Scienze 17A, 43124 Parma, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pelosi
authors.affiliation: Dipartimento di Bioscienze, Università degli Studi di Parma, Parco Area delle Scienze 11A, 43124 Parma, Italy. Electronic address: annamaria.buschini@unipr.it.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Buschini
authors.affiliation: Ecole Normale Supérieure, Département Chimie, 24 rue Lhomond, F-75005 Paris France; Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 Place Jussieu, 75005 Paris, France; Laboratoire des BioMolécules, UMR7203, CNRS, France. Electronic address: clotilde.policar@ens.fr.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Policar
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001059:Apoproteins / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry*; D056831:Coordination Complexes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D003300:Copper / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006017:Glycolipids / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D009353:Zinostatin / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D001059:Apoproteins; D001426:Bacterial Proteins; D056831:Coordination Complexes; D004337:Drug Carriers; D006017:Glycolipids; D003300:Copper; D009353:Zinostatin
keywords: Antiproliferative activity; Apo-neocarzinostatine; Carriers; Copper complexes; Glycoligands; Intracellular delivery