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Cancer Invest ; 23(5): 404-12, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16193640

RESUMO

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.


Assuntos
Leucemia Mieloide/metabolismo , NF-kappa B/metabolismo , Precursores de Proteínas/metabolismo , Pirrolidinas/toxicidade , Tiocarbamatos/toxicidade , Doença Aguda , Adolescente , Adulto , Apoptose , DNA/metabolismo , Feminino , Humanos , Leucemia Mieloide/genética , Masculino , Pessoa de Meia-Idade , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , Subunidade p50 de NF-kappa B , Oligonucleotídeos Antissenso/genética , Oligonucleotídeos Antissenso/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , Biossíntese de Proteínas/genética , Precursores de Proteínas/antagonistas & inibidores , Precursores de Proteínas/genética , Células Tumorais Cultivadas
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