Papel de fosfatases na viabilidade de celulas da leucemia mieloide humana tratadas com diterpeno lactona

AUTOR(ES)
DATA DE PUBLICAÇÃO

2002

RESUMO

patient with acute myeloid leukemia. This culture proliferates continuously in suspension and predominantly consists of promyelocytes and has been used as tool for cytotoxic studies of drugs, differentiation and cell death. ln this work was evaluated the cytotoxicity of protein phosphatases inhibitors (okadaic acid and pervanadate) and dehydrocrotonin (tDCTN) through following viability parameters, after 24h of the cells treatment: MTT reduction (mitochondrial integrity), protein determination (cell number indication) and fosfatase activity (cell metabolism). Both inhibitors presented cytotoxic effect on HL60 cells. In relation to mitochondrial function and phosphatase activity, these cells presented only 20% of viability in presence of okadaic acid (100 nM) and pervanadate (200 1lM). For t-DCTN were obtained the following IC50 values: 500 and 300 mM for protein content and MTT reduction, respectively. Other approached aspect was the relation to cellular redox state with a possible differentiation and cell death induction. For this purpose were determined: NBT reduction, DNA fragmentation, the loss of plasma membrane asymmetry and total GSH. t-DCTN presented low capacity of differentiation induction (20%). However, in the presence of protein phosphatase inhibitors this effect was not observed. Apoptosis was induced when the cells were treated with okadaic acid (34%) and plus t-DCTN this effect was increased (65,28%). According to the results obtained, we can suggest the importance of chemical modulation of protein phosphatases in several cellular processes, since cytotoxic effects presented by these compounds could be explained by redox state changing and/or direct effect (adducts formation) on these enzymes or other macromolecules

ASSUNTO(S)

fosfatases leucemia apoptose

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