title: Effect of MRJF4 on C6 Glioma Cells Proliferation and Migration.
abstract: BACKGROUND
  MRJF4, a novel haloperidol metabolite II prodrug, was obtained through the esterification of the secondary hydroxyl group of haloperidol metabolite II with 4-phenylbutyric acid. The activities of (±)-MRJF4 and its two enantiomers [(+)-MRJF4 and (-)-MRJF4] as tumor specific inducers of pro-apoptotic genes were evaluated on malignant C6 glioma cells. In particular, changes in Nf-κB signaling pathway, activity of nitric oxide synthases (NOS), metalloproteinases (MMPs), and membrane adhesion proteins were investigated.
  
  
  RESULTS
  IκBα reduced phosphorylation and iNOS lowered activity could be correlated with the previously demonstrated decreased proliferation and tumor progression of C6 cells upon 24 h of treatment with all the three compounds. Integrin β1 decreased expression, at the same experimental time, seems to support lower C6 cells migrative capability and the consequent reduced invasiveness of these cells upon treatment with (±)-MRJF4 and its enantiomers.
  
  
  CONCLUSIONS
  These results suggest that this multi-target prodrug and its two enantiomers might be a valuable clinical tool for the treatment of metastatic glioblastoma.
authors.affiliation: Department of Pharmacy, University G. d' Annunzio, Via dei Vestini, 66100 Chieti, Italy.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Pacella
authors.affiliation: Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, 630 W 168th St., New York, NY 10032. United States.
authors.forename: Jole
authors.initials: J
authors.lastname: Fiorito
authors.affiliation: Department of Pharmacy, University G. d' Annunzio, Via dei Vestini, 66100 Chieti, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Cacciatore
authors.affiliation: Department of Pharmacy, University G. d' Annunzio, Via dei Vestini, 66100 Chieti, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: di Giacomo
authors.affiliation: Department of Medicine and Aging Sciences, Via dei Vestini, 66100 Chieti, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Patruno
authors.affiliation: Institute of Molecular Genetics of CNR, 66100 Chieti, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Rapino
authors.affiliation: Department of Pharmacy, University G. d' Annunzio, Via dei Vestini, 66100 Chieti, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Stefano
authors.affiliation: Department of Pharmacy, University G. d' Annunzio, Via dei Vestini, 66100 Chieti, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Marinelli
authors.affiliation: Department of Pharmacy, University G. d' Annunzio, Via dei Vestini, 66100 Chieti, Italy.
authors.forename: Erika
authors.initials: E
authors.lastname: Fornasari
authors.affiliation: Department of Pharmacy, University G. d' Annunzio, Via dei Vestini, 66100 Chieti, Italy.
authors.forename: Amelia
authors.initials: A
authors.lastname: Cataldi
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry Section, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Prezzavento
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry Section, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
authors.forename: Agostino
authors.initials: A
authors.lastname: Marrazzo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010654:Phenylbutyrates / Q000494:pharmacology* / Q000627:therapeutic use; D011355:Prodrugs / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats
chemical_list: C556911:4-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)-1-(4-fluorophenyl)butyl 4-phenylbutyrate; D016328:NF-kappa B; D010654:Phenylbutyrates; D011355:Prodrugs; D006220:Haloperidol
keywords: C6 cells; MRJF4; NF-κB; histone deacetylase inhibitor; migration; proliferation