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.
Synthesis, characterization, and biological activity of a new water-soluble Pd(II)-deoxyalliin (S-allyl-Lcysteine) complex are described in this article. Elemental and thermal analysis for the complex are consistent with the formula [Pd(C 6 H 10 NO 2 S) 2 ]. 13 C NMR, 1 H NMR, and IR spectroscopy show coordination of the ligand to Pd(II) through S and N atoms in a square planar geometry. Final residue of the thermal treatment was identified as a mixture of PdO and metallic Pd. Antiproliferative assays using aqueous solutions of the complex against HeLa and TM5 tumor cells showed a pronounced activity of the complex even at low concentrations. After incubation for 24 h, the complex induced cytotoxic effect over HeLa cells when used at concentrations higher than 0.40 mmol/L. At lower concentrations, the complex was nontoxic, indicating its action is probably due to cell cycle arrest, rather than cell death. In agreement with these results, the flow cytometric analysis indicated that after incubation for 24 h at low concentrations of the complex cells are arrested in G0/G1. Résumé :On décrit la synthèse, la caractérisation et l'activité biologique d'un nouveau complexe, soluble dans l'eau, de Pd(II)-désoxyalliine (S-allyl-L-cystéine). Les analyses élémentaire et thermique du complexe sont en accord avec la formule [Pd(C 6 H 10 NO 2 S) 2 ]. Les spectres de RMN du 13 C et du 1 H ainsi que la spectroscopie infrarouge permettent de montrer que la coordination du ligand au Pd(II) se fait par les atomes de soufre et d'azote dans une géométrie plan carré. Le résidu final du traitement thermique a été identifié comme un mélange de PdO et de Pd métallique. Des essais antiproliférations à l'aide de solutions aqueuses du complexe ont permis de démontrer l'activité prononcée du complexe contre les cellules cancéreuses HeLa et TM5, même à faibles concentrations. Après une incubation de 24 h, le complexe utilisé à des concentrations supérieures à 0,40 mmol/L induit un effet cytotoxique vis-à-vis des cellules HeLa. À des concentrations plus faibles, le complexe n'est pas toxique, ce qui indique que son action est probablement due à un arrêt du cycle cellulaire plutôt qu'à une mort de la cellule. En accord avec ces résultats, l'analyse de l'écoulement cytométrique indique que, après une incubation de 24 h à de faibles concentrations de complexe, les cellules de G0/G1 s'arrêtent.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.