title: Pyrrolidinedithiocarbamate induces apoptosis in human acute myelogenous leukemic cells affecting NF-kappaB activity.
abstract: Pyrrolidindithiocarbamate (PDTC), is a metal chelator widely used to study the activation of redox sensitive transcription factors. Recently it has been demonstrated that it manifests pro-oxidant properties. The nuclear factor-Kappa B (NF-kappaB) transcription factor can both promote cell survival and induce apoptosis depending on cell type and context in response to genotoxic stress. In our previous study we reported that in acute myelogenous leukemia CD34+ cells PDTC stimulates apoptosis, whereas in CD34+ cells of healthy volunteers PDTC was ineffective. This cytotoxicity was dependent on the generation of superoxide anion and oxidized glutathione. In this article we have shown that the pro-oxidant effect of PDTC in AML cells induces NF-kappaB activity. These findings imply a role for NF-kappaB in the survival of normal cells with respect to leukemic cells, suggesting that NF-kappaB activity and function differs according to tumor cell phenotype.
authors.affiliation: Department of Biomedical Sciences, University of Catania, Catania, Italy. lucmal@mbox.unict.it
authors.forename: Lucia
authors.initials: L
authors.lastname: Malaguarnera
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Pilastro
authors.forename: Luisa
authors.initials: L
authors.lastname: Vicari
authors.forename: Rosanna
authors.initials: R
authors.lastname: Dimarco
authors.forename: Livia
authors.initials: L
authors.lastname: Manzella
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palumbo
authors.forename: Angelo
authors.initials: A
authors.lastname: Messina
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D004247:DNA / Q000378:metabolism; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects / Q000235:genetics; D011498:Protein Precursors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011759:Pyrrolidines / Q000633:toxicity*; D013859:Thiocarbamates / Q000633:toxicity*; D014407:Tumor Cells, Cultured
chemical_list: D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D016376:Oligonucleotides, Antisense; D011498:Protein Precursors; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D004247:DNA