title: Gentamicin arrests cancer cell growth: the intriguing involvement of nuclear sphingomyelin metabolism.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Science, University of Perugia, Perugia 06122, Italy. codini@virgilio.it.
authors.forename: Michela
authors.initials: M
authors.lastname: Codini
authors.affiliation: Department of Pharmaceutical Science, University of Perugia, Perugia 06122, Italy. samuelacataldi@libero.it.
authors.forename: Samuela
authors.initials: S
authors.lastname: Cataldi
authors.affiliation: Department of Clinical and Biological Sciences, University of Udine, Udine 33100, Italy. ambesis@me.com.
authors.forename: Francesco Saverio
authors.initials: FS
authors.lastname: Ambesi-Impiombato
authors.affiliation: Laboratory of Nuclear Lipid BioPathology, CRABiON, Perugia 06122, Italy. andrylazza@gmail.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Lazzarini
authors.affiliation: Laboratory of Nuclear Lipid BioPathology, CRABiON, Perugia 06122, Italy. info@crabion.it.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Floridi
authors.affiliation: Laboratory of Nuclear Lipid BioPathology, CRABiON, Perugia 06122, Italy. remo30@libero.it.
authors.forename: Remo
authors.initials: R
authors.lastname: Lazzarini
authors.affiliation: Department of Clinical and Biological Sciences, University of Udine, Udine 33100, Italy. curcio@uniud.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Curcio
authors.affiliation: Department of Pharmaceutical Science, University of Perugia, Perugia 06122, Italy. tommaso.beccari@unipg.it.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Beccari
authors.affiliation: Laboratory of Nuclear Lipid BioPathology, CRABiON, Perugia 06122, Italy. elisabetta.albi@yahoo.com.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Albi
mesh_terms: D000900:Anti-Bacterial Agents / Q000633:toxicity*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005839:Gentamicins / Q000633:toxicity*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005839:Gentamicins; D013109:Sphingomyelins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D013108:Sphingomyelin Phosphodiesterase