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Leuk Res ; 27(9): 823-9, 2003 Sep.
Article in English | MEDLINE | ID: mdl-12804641

ABSTRACT

Oxidative stress can be involved in several cellular responses, such as differentiation, apoptosis and necrosis. Dehydrocrotonin (DCTN, diterpene lactone) from Croton cajucara, Brazilian medicinal plant, slightly induced NBT-reducing activity. In presence of protein phosphatase inhibitors significant differentiation of HL60 cells was observed. Flow cytometry analysis demonstrated that apoptosis was induced when the cells were treated with okadaic acid (OKA) and plus trans-dehydrocrotonin (t-DCTN) this effect was two-fold increased. Unlike, when the cells were treated only with t-DCTN, necrosis was observed. On the other hand, the necrosis induced by t-DCTN could be due to oxidative stress, revealed by increase of GSH content. Therefore, this differentiation pathway involves the modulation of protein phosphatases and this inhibition promotes the t-DCTN action on apoptosis induction.


Subject(s)
Apoptosis/drug effects , Diterpenes, Clerodane , Diterpenes/pharmacology , Enzyme Inhibitors/pharmacology , Leukemia, Promyelocytic, Acute/metabolism , Okadaic Acid/pharmacology , Phosphoprotein Phosphatases/antagonists & inhibitors , Annexin A5/metabolism , Brazil , Cell Differentiation/drug effects , Croton , Drug Screening Assays, Antitumor , Flow Cytometry , Glutathione/metabolism , HL-60 Cells/pathology , Humans , Leukemia, Promyelocytic, Acute/pathology , Necrosis , Oxidative Stress/drug effects , Phosphoprotein Phosphatases/metabolism , Plants, Medicinal , Vanadates/pharmacology
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