Inhibition of eukaryotic translation initiation factor 5A (eIF5A) hypusination impairs melanoma growth |
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| Authors: | Jasiulionis Miriam G Luchessi Augusto D Moreira Andreia G Souza Pedro P C Suenaga Ana P M Correa Mariangela Costa Carlos A S Curi Rui Costa-Neto Claudio M |
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| Affiliation: | 1. Department of Micro‐Immuno‐Parasitology, Federal University of S?o Paulo, 04023‐062, S?o Paulo, Brazil;2. Department of Physiology and Biophysics—Institute of Biomedical Sciences—University of S?o Paulo, 05508‐900, S?o Paulo, Brazil;3. Department of Biochemistry and Immunology, Faculty of Medicine of Ribeir?o Preto—University of S?o Paulo, 14049‐900, Ribeir?o Preto, Brazil;4. Department of Physiology and Pathology, Faculty of Dentistry of Araraquara—UNESP, 14801‐903, Araraquara, Brazil |
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| 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. |
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| Keywords: | tumour growth cell proliferation melanoma cytotoxicity eIF5A eIF‐5A hypusine GC7 |
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