Influence of protein phosphatase inhibitors on HL60 cells death induction by dehydrocrotonin.
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.
Freire
Ana Claudia Galvão
AC
Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), CP 6109, 13083-970, São Paulo, Campinas, Brazil
de Assis
Cristiane Fernandes
CF
Frick
Alexander Otto
AO
da Silva Melo
Patrícia
P
Haun
Marcela
M
Aoyama
Hiroshi
H
Durán
Nelson
N
Sauer
Mariana Melillo
MM
Kallás
Esper Georges
EG
Ferreira
Carmen Veríssima
CV
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
D017304:Annexin A5; D004224:Diterpenes; D045785:Diterpenes, Clerodane; D004791:Enzyme Inhibitors; C103060:dehydrocrotonin; D019319:Okadaic Acid; D014638:Vanadates; D010749:Phosphoprotein Phosphatases; D005978:Glutathione