Antitubulinic effect of New Fluorazone Derivatives on Melanoma Cells

Title:Antitubulinic effect of New Fluorazone Derivatives on Melanoma Cells

Volume: 16 Issue: 5

Author(s): Claudia Sticozzi, Francesca Aiello, Rita Bassi Andreasi, Ximena Maria Muresan, Giuseppe Belmonte, Franco Cervellati, Emilia Maellaro, Emanuela Maioli and Giuseppe Valacchi

Affiliation:

Keywords: Cell cycle, cyclin D1, Glu-tubulin, microtubules, nitrotyrosin, skin.

Abstract: Microtubules are composed by α- and β-tubulin polypeptides. α-tubulin undergoes a reversible posttranslational modification whereby the C-terminal tyrosine residue is removed (Glu-tubulin) and re-added (Tyrtubulin). Recent studies have shown that α-tubulin tyrosine residues can be nitrated and the incorporation of NO₂Tyr into the C-terminus of Glu-tubulin forms a complex that blocks the tyrosination/detyrosination cycle, an event that can compromise protein/enzyme functions, such as cell division. Since many studies demonstrated that Glu-tubulin levels increase in cancer, the aim of the present study was to investigate the effect of new drugs, fluorazone derivatives (K1-K2-K9-K10-K11), on the proliferation of melanoma cells. Our results demonstrated that these drugs, except for K2, were able to inhibit cellular proliferation without exhibiting cytotoxicity. The anti-proliferative effect was accompanied by the decrease of Glu-tubulin levels and the increase of its nitration. This effect seems to be a consequence of NO₂ induction and NO2Tyr ligation to Glu-tubulin. Collectively, these results, showing that the fluorazone derivatives, by promoting NO₂Tyr incorporation into α-tubulin, are able to arrest the cycle of detyrosination/tyrosination and to inhibit cell proliferation, offer new perspectives for the possible usage of these drugs, alone or in combination, as non-toxic, anti-proliferative agents in melanoma.

Cite this article as:

Sticozzi Claudia, Aiello Francesca, Andreasi Bassi Rita, Muresan Maria Ximena, Belmonte Giuseppe, Cervellati Franco, Maellaro Emilia, Maioli Emanuela and Valacchi Giuseppe, Antitubulinic effect of New Fluorazone Derivatives on Melanoma Cells, Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (5) . https://dx.doi.org/10.2174/1871520615666150909120014