Influence of protein phosphatase inhibitors on HL60 cells death induction by dehydrocrotonin

Freire, Ana Claudia Galvão; de Assis, Cristiane Fernandes; Frick, Alexander Otto; da Silva Melo, Patrı́cia; Haun, Marcela; Aoyama, Hiroshi; Durán, Nelson; Sauer, Mariana Melillo; Kallás, Ésper Georges; Ferreira, Carmen Verı́ssima

doi:10.1016/S0145-2126(03)00013-4

« Previous Next »Leukemia Research
Volume 27, Issue 9 , Pages 823-829, September 2003

Influence of protein phosphatase inhibitors on HL60 cells death induction by dehydrocrotonin

Ana Claudia Galvão Freire
- Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), CP 6109, Campinas 13083-970, São Paulo, Brazil
Cristiane Fernandes de Assis
- Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), CP 6109, Campinas 13083-970, São Paulo, Brazil
Alexander Otto Frick
- Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), CP 6109, Campinas 13083-970, São Paulo, Brazil
Patrı́cia da Silva Melo
- Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), CP 6109, Campinas 13083-970, São Paulo, Brazil
Marcela Haun
- Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), CP 6109, Campinas 13083-970, São Paulo, Brazil
Hiroshi Aoyama
- Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), CP 6109, Campinas 13083-970, São Paulo, Brazil
Nelson Durán
- Biological Chemistry Laboratory, Institute of Chemistry, State University of Campinas (UNICAMP), CP 6154, Campinas 13081-970, São Paulo, Brazil
Mariana Melillo Sauer
- Department of Infectoparasitaries Diseases (DIPA), Immunology Laboratory, EPM/UNIFESP, São Paulo, Brazil
Ésper Georges Kallás
- Department of Infectoparasitaries Diseases (DIPA), Immunology Laboratory, EPM/UNIFESP, São Paulo, Brazil
Carmen Verı́ssima Ferreira
- Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), CP 6109, Campinas 13083-970, São Paulo, Brazil
- Corresponding author. Fax: +55-19-3788-3124.

Received 16 August 2002; accepted 21 December 2002.

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.

Keywords: Pervanadate, Okadaic acid, Dehydrocrotonin, HL60, Protein phosphatase, Glutathione, Differentiation, Apoptosis