title: Influence of protein phosphatase inhibitors on HL60 cells death induction by dehydrocrotonin.
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.
authors.affiliation: Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), CP 6109, 13083-970, São Paulo, Campinas, Brazil
authors.forename: Ana Claudia Galvão
authors.initials: AC
authors.lastname: Freire
authors.forename: Cristiane Fernandes
authors.initials: CF
authors.lastname: de Assis
authors.forename: Alexander Otto
authors.initials: AO
authors.lastname: Frick
authors.forename: Patrícia
authors.initials: P
authors.lastname: da Silva Melo
authors.forename: Marcela
authors.initials: M
authors.lastname: Haun
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aoyama
authors.forename: Nelson
authors.initials: N
authors.lastname: Durán
authors.forename: Mariana Melillo
authors.initials: MM
authors.lastname: Sauer
authors.forename: Esper Georges
authors.initials: EG
authors.lastname: Kallás
authors.forename: Carmen Veríssima
authors.initials: CV
authors.lastname: Ferreira
mesh_terms: D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D001938:Brazil; D002454:Cell Differentiation / Q000187:drug effects; D029802:Croton; D004224:Diterpenes / Q000494:pharmacology*; D045785:Diterpenes, Clerodane; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005434:Flow Cytometry; D005978:Glutathione / Q000378:metabolism; D018922:HL-60 Cells / Q000473:pathology; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D019319:Okadaic Acid / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010946:Plants, Medicinal; D014638:Vanadates / Q000494:pharmacology
chemical_list: D017304:Annexin A5; D004224:Diterpenes; D045785:Diterpenes, Clerodane; D004791:Enzyme Inhibitors; C103060:dehydrocrotonin; D019319:Okadaic Acid; D014638:Vanadates; D010749:Phosphoprotein Phosphatases; D005978:Glutathione