title: Inhibition of eukaryotic translation initiation factor 5A (eIF5A) hypusination impairs melanoma growth.
abstract: The eukaryotic translation initiation factor 5A (eIF5A) undergoes a specific post-translational modification called hypusination. This modification is required for the functionality of this protein. The compound N1-guanyl-1,7-diaminoheptane (GC7) is a potent and selective inhibitor of deoxyhypusine synthase, which catalyses the first step of eIF5A hypusination process. In the present study, the effects of GC7 on cell death were investigated using two cell lines: melan-a murine melanocytes and Tm5 murine melanoma. In vitro treatment with GC7 increased by 3-fold the number of cells presenting DNA fragmentation in Tm5 cells. Exposure to GC7 also decreased viability to both cell lines. This study also describes, for the first time, the in vivo antitumour effect of GC7, as indicated by impaired melanoma growth in C57BL/6 mice.
authors.affiliation: Department of Micro-Immuno-Parasitology, Federal University of São Paulo, 04023-062, São Paulo, Brazil.
authors.forename: Miriam G
authors.initials: MG
authors.lastname: Jasiulionis
authors.forename: Augusto D
authors.initials: AD
authors.lastname: Luchessi
authors.forename: Andreia G
authors.initials: AG
authors.lastname: Moreira
authors.forename: Pedro P C
authors.initials: PP
authors.lastname: Souza
authors.forename: Ana P M
authors.initials: AP
authors.lastname: Suenaga
authors.forename: Mariangela
authors.initials: M
authors.lastname: Correa
authors.forename: Carlos A S
authors.initials: CA
authors.lastname: Costa
authors.forename: Rui
authors.initials: R
authors.lastname: Curi
authors.forename: Claudio M
authors.initials: CM
authors.lastname: Costa-Neto
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D010448:Peptide Initiation Factors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D006147:Guanine; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C100667:N(1)-guanyl-1,7-diaminoheptane