Hypusine amino acid [Nε-(4-amino-2-hydroxybutyl)-
lysine] was first isolated in 1971 from bovine brain extracts.
Hypusine originates from a post-translational modification at the
eukaryotic translation initiation factor 5A (eIF5A), a
protein produced by archaebacteria and eukaryotes. The
eIF5A protein is the only one described containing the
hypusine residue, which is essential for its activity.
Hypusine as a free
amino acid is a consequence of proteolytic degradation of eIF5A. Herein, we showed, for the first time, evidence of
biological activity for the free
hypusine. C6 rat
glioma cells were treated with
hypusine, and different cellular parameters were evaluated.
Hypusine treatment significantly reduced C6 cell proliferation and potently suppressed their clonogenic capacity without leading to apoptosis.
Hypusine also decreased the Eif5A transcript content and the global
protein synthesis profile that may occur due to negative feedback in response to high
hypusine concentration, controlling the content of newly synthesized eIF5A, which can affect the translation process. Besides,
hypusine treatment also altered cellular metabolism by changing the pathways for energy production, reducing cellular respiration coupled with oxidative phosphorylation, and increasing the anaerobic metabolism. These observed results and the relationship between eIF5A and
tumor processes led us to test the combination of
hypusine with the chemotherapeutic
drug temozolomide. Combining
temozolomide with
hypusine reduced the MTT conversion to the same levels as those observed using double
temozolomide dosage alone, demonstrating a synergetic action between the compounds. Thus, since 1971, this is the first study showing evidence of
biological activity for
hypusine not associated with being an essential component of the
eiF5A protein. Finding out the molecular targets of
hypusine are the following efforts to completely characterize its
biological activity.