Inhibition of eukaryotic translation initiation factor 5A (eIF5A) hypusination impairs melanoma growth.
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.
Jasiulionis
Miriam G
MG
Department of Micro-Immuno-Parasitology, Federal University of São Paulo, 04023-062, São Paulo, Brazil.
Luchessi
Augusto D
AD
Moreira
Andreia G
AG
Souza
Pedro P C
PP
Suenaga
Ana P M
AP
Correa
Mariangela
M
Costa
Carlos A S
CA
Curi
Rui
R
Costa-Neto
Claudio M
CM
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
D006147:Guanine; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D000097574:Eukaryotic Translation Initiation Factor 5A; C100667:N(1)-guanyl-1,7-diaminoheptane