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CELL DEATH DISCOVERY, 6(1), 9.";s:4:"data";s:4:"2020";s:2:"id";s:20:"PUBBLICAZIONE_382595";s:6:"handle";s:11:"2108/241292";s:9:"metadata1";s:19:"Articolo su rivista";s:9:"metadata2";s:36:"Cancer therapy; Preclinical research";s:9:"metadata3";s:14:"Settore MED/07";s:9:"metadata4";s:2052:"Adult T cell leukemia/lymphoma (ATL) can be susceptible, at least transiently, to treatments with azidothymidine (AZT) plus IFNα and/or arsenic trioxide. However, the real role of AZT in this effect is still unclear. In fact, while reverse transcriptase (RT) inhibition could explain reduction of clonal expansion and of renewal of HTLV-1 infected cells during ATL progression, this effect alone seems insufficient to justify the evident and prompt decrease of the pro-viral load in treated patients. We have previously demonstrated that AZT is endowed with an intrinsic pro-apoptotic potential towards both peripheral blood mononuclear cells from healthy donors or some tumor cell lines, but this cytotoxic potential cannot be fully achieved unless IκBα phosphorylation is inhibited. Since the constitutive activation of NF-kappa B (NF-κB) appears a common biological basis of HTLV-1-infected cells, a pharmacological inhibition of IκBα phosphorylation seems a potential strategy for treating and preventing HTLV-1 related pathologies. In this study, we have demonstrated that a combination treatment with the IκBα phosphorylation inhibitor Bay 11-7085 and AZT induced increased levels of regulated cell death (RCD) by apoptosis compared to the single treatments in HTLV-1 infected cells of different origin. Importantly, levels of RCD were considerably higher in infected cells in comparison with the uninfected ones. Inhibition of NF-κB activation following the combined treatment was confirmed by analysis of both gel-shift and functional activity of the NF-κB complex proteins, p65/p52. Moreover, a transcriptional analysis revealed that the addition of Bay 11-7085 to AZT treatment in HTLV-1-infected cells modified their transcriptional profile, by inducing the upregulation of some pro-apoptotic genes together with the downregulation of some anti-apoptotic genes. Our data suggest that addition of adequate concentrations of IκBα phosphorylation inhibitor to therapeutic regimens including AZT could be a promising strategy in ATL.";s:9:"metadata5";s:120:"Inhibition of IκBα phosphorylation potentiates regulated cell death induced by azidothymidine in HTLV-1 infected cells";s:9:"metadata6";s:105:"Matteucci, C; Marino-Merlo, F; Minutolo, A; Balestrieri, E; Valletta, E; Macchi, B; Mastino, A; Grelli, S";s:9:"metadata7";s:25:"10.1038/s41420-020-0243-x";s:9:"metadata8";N;s:9:"metadata9";N;s:10:"metadata10";N;}i:1;a:14:{s:9:"citazione";s:278:"Memeo, M.g., Valletta, E., Macchi, B., Porta, A., Bovio, B., Moiola, M., et al. (2018). Ene Reaction of Nitrosocarbonyl Mesitylene with the Cinnamyl Alcohol: Metabolic Activity and Apoptosis of the Synthetized 6-Chloropurine N,O-Nucleoside Analogues. ACS OMEGA, 3(7), 7621-7629.";s:4:"data";s:10:"2018-07-10";s:2:"id";s:20:"PUBBLICAZIONE_343926";s:6:"handle";s:11:"2108/208949";s:9:"metadata1";s:19:"Articolo su rivista";s:9:"metadata2";N;s:9:"metadata3";s:34:"Settore CHIM/06 - Chimica Organica";s:9:"metadata4";N;s:9:"metadata5";s:161:"Ene Reaction of Nitrosocarbonyl Mesitylene with the Cinnamyl Alcohol: Metabolic Activity and Apoptosis of the Synthetized 6-Chloropurine N,O-Nucleoside Analogues";s:9:"metadata6";s:78:"Memeo, Mg; Valletta, E; Macchi, B; Porta, A; Bovio, B; Moiola, M; Quadrelli, P";s:9:"metadata7";s:24:"10.1021/acsomega.8b00970";s:9:"metadata8";N;s:9:"metadata9";N;s:10:"metadata10";N;}i:2;a:14:{s:9:"citazione";s:231:"Valletta, E., Rinaldi, A., Marini, M., Franzese, O., & Roscetti, G. (2018). Distinct Hypericum perforatum L. total extracts exert different antitumour activity on erythroleukemic K562 cells. PHYTOTHERAPY RESEARCH, 32(9), 1803-1811.";s:4:"data";s:4:"2018";s:2:"id";s:20:"PUBBLICAZIONE_354771";s:6:"handle";s:11:"2108/217866";s:9:"metadata1";s:19:"Articolo su rivista";s:9:"metadata2";N;s:9:"metadata3";s:14:"Settore BIO/09";s:9:"metadata4";N;s:9:"metadata5";s:113:"Distinct Hypericum perforatum L. total extracts exert different antitumour activity on erythroleukemic K562 cells";s:9:"metadata6";s:60:"Valletta, E; Rinaldi, A; Marini, M; Franzese, O; Roscetti, G";s:9:"metadata7";s:16:"10.1002/ptr.6114";s:9:"metadata8";N;s:9:"metadata9";N;s:10:"metadata10";N;}i:3;a:14:{s:9:"citazione";s:308:"Marino-Merlo, F., Frezza, C., Papaianni, E., Valletta, E., Mastino, A., & Macchi, B. (2017). Development and evaluation of a simple and effective RT-qPCR inhibitory assay for detection of the efficacy of compounds towards HIV reverse transcriptase. 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