title: Lipid-Conjugation of Endogenous Neuropeptides: Improved Biotherapy against Human Pancreatic Cancer.
abstract: Neuropeptides are small neuronal signaling molecules that act as neuromodulators for a variety of neural functions including analgesia, reproduction, social behavior, learning, and memory. One of the endogenous neuropeptides-Met-Enkephalin (Met-Enk), has been shown to display an inhibitory effect on cell proliferation and differentiation. Here, a novel lipid-modification approach is shown to create a small library of neuropeptides that will allow increased bioavailability and plasma stability after systemic administration. It is demonstrated, on an experimental model of human pancreatic adenocarcinoma, that lipid conjugation of Met-Enk enhances its tumor suppression efficacy compared to its nonlipidated counterparts, both in vitro and in vivo. More strikingly, the in vivo studies show that a combination therapy with a reduced concentration of Gemcitabine has suppressed the tumor growth considerably even three weeks after the last treatment.
authors.affiliation: Institut Galien Paris-Sud (UMR CNRS 8612), Faculté de Pharmacie, Université Paris-Sud, 92296, Châtenay Malabry, France.
authors.forename: Gopakumar
authors.initials: G
authors.lastname: Gopalakrishnan
authors.affiliation: Institut Galien Paris-Sud (UMR CNRS 8612), Faculté de Pharmacie, Université Paris-Sud, 92296, Châtenay Malabry, France.
authors.forename: Sinda
authors.initials: S
authors.lastname: Lepetre
authors.affiliation: Institut Galien Paris-Sud (UMR CNRS 8612), Faculté de Pharmacie, Université Paris-Sud, 92296, Châtenay Malabry, France.
authors.forename: Andrei
authors.initials: A
authors.lastname: Maksimenko
authors.affiliation: Institut Galien Paris-Sud (UMR CNRS 8612), Faculté de Pharmacie, Université Paris-Sud, 92296, Châtenay Malabry, France.
authors.forename: Simona
authors.initials: S
authors.lastname: Mura
authors.affiliation: Institut Galien Paris-Sud (UMR CNRS 8612), Faculté de Pharmacie, Université Paris-Sud, 92296, Châtenay Malabry, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Desmaële
authors.affiliation: Institut Galien Paris-Sud (UMR CNRS 8612), Faculté de Pharmacie, Université Paris-Sud, 92296, Châtenay Malabry, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
mesh_terms: D000818:Animals; D001691:Biological Therapy / Q000379:methods; D045744:Cell Line, Tumor; D019073:HT29 Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry* / Q000494:pharmacology*; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D009479:Neuropeptides / Q000737:chemistry* / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*
chemical_list: D008055:Lipids; D009479:Neuropeptides
keywords: lipids; met-enkephalin; neuropeptides; pancreatic cancer; squalene