Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/201208
Type: Artigo de periódico
Title: Differential Effects Of Nitrostyrene Derivatives On Myelopoiesis Involve Regulation Of C/ebpα And P38mapk Activity.
Author: Bartels, Marije
Calgarotto, Andrana K
Martens, Anton C
Maso, Victor
da Silva, Saulo L
Bierings, Marc B
de Souza Queiroz, Mary L
Coffer, Paul J
Abstract: Bone marrow failure syndromes and MDS represent a heterogenous group of diseases, characterized by ineffective myelopoiesis, the risk of clonal evolution and a generally poor response to chemotherapy-based treatment regimen. Nitrostyrene derivatives have been studied as protein phosphatase inhibitors in various tumor models. Pharmacological studies have identified nitrostyrene as the structural core underlying a pro-apoptotic effect in tumor cells, yet their effects on normal cells, including those of the hematopoietic system, are largely unknown. In this study, utilizing umbilical cord blood-derived myeloid progenitor cells, patient-derived bone marrow cells, and a (BALB/c) mouse model; we investigated the effects of treatment with two nitrostyrene derivatives (NTS1 and NTS2) on myeloid development. We demonstrate that these compounds stimulate the expansion and differentiation of myeloid progenitors in vitro and improve myeloid reconstitution after chemotherapy-induced bone marrow depletion in vitro and in vivo. These effects were accompanied by increased C/EBPα expression and activity and inhibition of the p38MAPK signalling pathway. Together, our data suggest that nitrostyrenes improve myelopoiesis and represent potential new treatment strategies for patients suffering from bone marrow failure syndromes, hypocellular myelodysplastic syndrome and chemotherapy-induced aplasia.
Rights: aberto
Identifier DOI: 10.1371/journal.pone.0090586
Address: http://www.ncbi.nlm.nih.gov/pubmed/24614182
Date Issue: 2014
Appears in Collections:Unicamp - Artigos e Outros Documentos

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