title: Formulation and in vitro efficacy of liposomes containing the Hsp90 inhibitor 6BrCaQ in prostate cancer cells.
abstract: 6BrCaQ is a promising anti-cancer agent derived from novobiocin, which has been shown to inhibit Hsp90. 6BrCaQ was loaded into nanometer-scaled phospholipid vesicles (liposomes) suitable for drug delivery to solid tumors. The effective incorporation of the drug within the phospholipid bilayer was investigated by differential scanning calorimetry. Liposomal 6BrCaQ showed good activity on PC-3 cell lines in vitro in terms of apoptosis induction and cell growth arrest in G2/M. Liposomes containing 6BrCaQ were also shown to slow down migration of PC-3 cells in presence of chemokine ligand 2 and to synergize with doxorubicin. Several Hsp90 targeting molecules like geldanamycin induce accumulation of Hsp70, leading to cytoprotection and often correlated with poor prognosis. In this study, we did not report any Hsp70 induction after treatment with liposomal 6BrCaQ but a decrease in Hsp90 and CDK-4 protein expression, indicating an effect on the chaperon machinery. Liposomal encapsulation of 6BrCaQ revealed promising anti-cancer effects and a better understanding of its mechanism of action.
authors.affiliation: Institut Galien Paris-Sud, CNRS, UMR 8612, Université Paris-Sud, Université Paris-Saclay, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: Félix
authors.initials: F
authors.lastname: Sauvage
authors.affiliation: Institut Galien Paris-Sud, CNRS, UMR 8612, Université Paris-Sud, Université Paris-Saclay, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.-B. Clément, Châtenay-Malabry F-92296, France; Università degli Studi di Milano, Department of Pharmaceutical Sciences, via G. Colombo 71, 20133 Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Franzè
authors.affiliation: CNRS, BioCIS-UMR 8076, Laboratoire de Chimie Thérapeutique, Equipe Labellisée Ligue Contre Le Cancer, Université Paris-Sud, Université Paris-Saclay, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bruneau
authors.affiliation: CNRS, BioCIS-UMR 8076, Laboratoire de Chimie Thérapeutique, Equipe Labellisée Ligue Contre Le Cancer, Université Paris-Sud, Université Paris-Saclay, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: Mouad
authors.initials: M
authors.lastname: Alami
authors.affiliation: Institut Galien Paris-Sud, CNRS, UMR 8612, Université Paris-Sud, Université Paris-Saclay, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Denis
authors.affiliation: Plateforme d'imagerie cellulaire MIPSIT, SFR-UMS-IPSIT, Université Paris-Sud, Université Paris-Saclay, Faculté de Pharmacie, 5 rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Nicolas
authors.affiliation: Institut Galien Paris-Sud, CNRS, UMR 8612, Université Paris-Sud, Université Paris-Saclay, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: Sylviane
authors.initials: S
authors.lastname: Lesieur
authors.affiliation: Institut Galien Paris-Sud, CNRS, UMR 8612, Université Paris-Sud, Université Paris-Saclay, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Legrand
authors.affiliation: Institut Galien Paris-Sud, CNRS, UMR 8612, Université Paris-Sud, Université Paris-Saclay, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: Gillian
authors.initials: G
authors.lastname: Barratt
authors.affiliation: CNRS, BioCIS-UMR 8076, Laboratoire de Chimie Thérapeutique, Equipe Labellisée Ligue Contre Le Cancer, Université Paris-Sud, Université Paris-Saclay, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.-B. Clément, Châtenay-Malabry F-92296, France.
authors.forename: Samir
authors.initials: S
authors.lastname: Messaoudi
authors.affiliation: Institut Galien Paris-Sud, CNRS, UMR 8612, Université Paris-Sud, Université Paris-Saclay, LabEx LERMIT, Faculté de Pharmacie, 5 rue J.-B. Clément, Châtenay-Malabry F-92296, France. Electronic address: juliette.vergnaud@u-psud.fr.
authors.forename: Juliette
authors.initials: J
authors.lastname: Vergnaud-Gauduchon
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems; D004357:Drug Synergism; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D008081:Liposomes; D008297:Male; D010743:Phospholipids / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C560164:3-aminoquinolein-2-one; D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D008081:Liposomes; D010743:Phospholipids; D015363:Quinolones; D004317:Doxorubicin
keywords: Apoptosis; Cell cycle; Hsp90; Liposomes; Migration; Novobiocin analog