Pyrrolidinedithiocarbamate induces apoptosis in human acute myelogenous leukemic cells affecting NF-kappaB activity.
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.
Malaguarnera
Lucia
L
Department of Biomedical Sciences, University of Catania, Catania, Italy. lucmal@mbox.unict.it
Pilastro
Maria Rosaria
MR
Vicari
Luisa
L
Dimarco
Rosanna
R
Manzella
Livia
L
Palumbo
Giuseppe
G
Messina
Angelo
A
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
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