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Gentamicin Arrests Cancer Cell Growth: The Intriguing Involvement of Nuclear Sphingomyelin Metabolism

The use of gentamicin for the treatment of bacterial infection has always been an interesting and highly speculated issue for the scientific community. Conversely, its effect on cancer cells has been very little investigated. We studied the effect of high doses of gentamicin on non-Hodgkin’s T-cell...

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Autores principales: Codini, Michela, Cataldi, Samuela, Ambesi-Impiombato, Francesco Saverio, Lazzarini, Andrea, Floridi, Alessandro, Lazzarini, Remo, Curcio, Francesco, Beccari, Tommaso, Albi, Elisabetta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346838/
https://www.ncbi.nlm.nih.gov/pubmed/25622250
http://dx.doi.org/10.3390/ijms16022307
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author Codini, Michela
Cataldi, Samuela
Ambesi-Impiombato, Francesco Saverio
Lazzarini, Andrea
Floridi, Alessandro
Lazzarini, Remo
Curcio, Francesco
Beccari, Tommaso
Albi, Elisabetta
author_facet Codini, Michela
Cataldi, Samuela
Ambesi-Impiombato, Francesco Saverio
Lazzarini, Andrea
Floridi, Alessandro
Lazzarini, Remo
Curcio, Francesco
Beccari, Tommaso
Albi, Elisabetta
author_sort Codini, Michela
collection PubMed
description The use of gentamicin for the treatment of bacterial infection has always been an interesting and highly speculated issue for the scientific community. Conversely, its effect on cancer cells has been very little investigated. We studied the effect of high doses of gentamicin on non-Hodgkin’s T-cell human lymphoblastic lymphoma (SUP-T1). We showed that gentamicin delayed cell growth and induced cell death in lymphoma cells with a rather mild effect on lymphocytes. In SUP-T1 cells, GAPDH, B2M, CDKN1A and CDKN1B were down-expressed in comparison with lymphocytes. Gentamicin treatment in SUP-T1 cells restored the expression of GAPDH, B2M and CDKN1A to values similar to those of lymphocytes and caused overexpression of CDKN1B. The drug acted via sphingomyelin metabolism; in whole cells, sphingomyelinase activity was stimulated, whereas in purified nuclei, sphingomyelinase activity was inhibited and that of sphingomyelin-synthase was stimulated, with a consequent high level of nuclear sphingomyelin content. We suggest that the increase of nuclear sphingomyelin might enrich the nucleus of lipid microdomains that act as a platform for active chromatin and, thus, might be responsible for gene expression. It is possible that in lymphoblastic lymphoma, high doses of gentamicin induce a beneficial therapeutic outcome.
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spelling pubmed-43468382015-04-03 Gentamicin Arrests Cancer Cell Growth: The Intriguing Involvement of Nuclear Sphingomyelin Metabolism Codini, Michela Cataldi, Samuela Ambesi-Impiombato, Francesco Saverio Lazzarini, Andrea Floridi, Alessandro Lazzarini, Remo Curcio, Francesco Beccari, Tommaso Albi, Elisabetta Int J Mol Sci Article The use of gentamicin for the treatment of bacterial infection has always been an interesting and highly speculated issue for the scientific community. Conversely, its effect on cancer cells has been very little investigated. We studied the effect of high doses of gentamicin on non-Hodgkin’s T-cell human lymphoblastic lymphoma (SUP-T1). We showed that gentamicin delayed cell growth and induced cell death in lymphoma cells with a rather mild effect on lymphocytes. In SUP-T1 cells, GAPDH, B2M, CDKN1A and CDKN1B were down-expressed in comparison with lymphocytes. Gentamicin treatment in SUP-T1 cells restored the expression of GAPDH, B2M and CDKN1A to values similar to those of lymphocytes and caused overexpression of CDKN1B. The drug acted via sphingomyelin metabolism; in whole cells, sphingomyelinase activity was stimulated, whereas in purified nuclei, sphingomyelinase activity was inhibited and that of sphingomyelin-synthase was stimulated, with a consequent high level of nuclear sphingomyelin content. We suggest that the increase of nuclear sphingomyelin might enrich the nucleus of lipid microdomains that act as a platform for active chromatin and, thus, might be responsible for gene expression. It is possible that in lymphoblastic lymphoma, high doses of gentamicin induce a beneficial therapeutic outcome. MDPI 2015-01-22 /pmc/articles/PMC4346838/ /pubmed/25622250 http://dx.doi.org/10.3390/ijms16022307 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Codini, Michela
Cataldi, Samuela
Ambesi-Impiombato, Francesco Saverio
Lazzarini, Andrea
Floridi, Alessandro
Lazzarini, Remo
Curcio, Francesco
Beccari, Tommaso
Albi, Elisabetta
Gentamicin Arrests Cancer Cell Growth: The Intriguing Involvement of Nuclear Sphingomyelin Metabolism
title Gentamicin Arrests Cancer Cell Growth: The Intriguing Involvement of Nuclear Sphingomyelin Metabolism
title_full Gentamicin Arrests Cancer Cell Growth: The Intriguing Involvement of Nuclear Sphingomyelin Metabolism
title_fullStr Gentamicin Arrests Cancer Cell Growth: The Intriguing Involvement of Nuclear Sphingomyelin Metabolism
title_full_unstemmed Gentamicin Arrests Cancer Cell Growth: The Intriguing Involvement of Nuclear Sphingomyelin Metabolism
title_short Gentamicin Arrests Cancer Cell Growth: The Intriguing Involvement of Nuclear Sphingomyelin Metabolism
title_sort gentamicin arrests cancer cell growth: the intriguing involvement of nuclear sphingomyelin metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346838/
https://www.ncbi.nlm.nih.gov/pubmed/25622250
http://dx.doi.org/10.3390/ijms16022307
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