Mangiferin activates Nrf2-antioxidant response element signaling without reducing the sensitivity to etoposide of human myeloid leukemia cells in vitro.
Acta Pharmacol Sin
; 35(2): 257-66, 2014 Feb.
Article
em En
| MEDLINE
| ID: mdl-24374812
ABSTRACT
AIM:
Mangiferin is glucosylxanthone extracted from plants of the Anacardiaceae and Gentianaceae families. The aim of this study was to investigate the effects of mangiferin on Nrf2-antioxidant response element (ARE) signaling and the sensitivity to etoposide of human myeloid leukemia cells in vitro.METHODS:
Human HL-60 myeloid leukemia cells and mononuclear human umbilical cord blood cells (MNCs) were examined. Nrf2 protein was detected using immunofluorescence staining and Western blotting. Binding of Nrf2 to ARE was examined with electrophoretic mobility shift assay. The level of NQO1 was assessed with real-time RT-PCR and Western blotting. DCFH-DA was used to evaluate intracellular ROS level. Cell proliferation and apoptosis were analyzed using MTT and flow cytometry, respectively.RESULTS:
Mangiferin (50 µmol/L) significantly increased Nrf2 protein accumulation in HL-60 cells, particularly in the nucleus. Mangiferin also enhanced the binding of Nrf2 to an ARE, significantly up-regulated NQO1 expression and reduced intracellular ROS in HL60 cells. Mangiferin alone dose-dependently inhibited the proliferation of HL-60 cells. Mangiferin (50 mol/L) did not attenuate etoposide-induced cytotoxicity in HL-60 cells, and combined treatment of mangiferin with low concentration of etoposide (0.8 µg/mL) even increased the cell inhibition rate. Nor did mangiferin change the rate of etoposide-induced apoptosis in HL-60 cells. In MNCs, mangiferin significantly relieved oxidative stress, but attenuated etoposide-induced cytotoxicity.CONCLUSION:
Mangiferin is a novel Nrf2 activator that reduces oxidative stress and protects normal cells without reducing the sensitivity to etoposide of HL-60 leukemia cells in vitro. Mangiferin may be a potential chemotherapy adjuvant.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Leucemia Mieloide
/
Xantonas
/
Fator 2 Relacionado a NF-E2
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Etoposídeo
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Elementos de Resposta Antioxidante
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
Acta Pharmacol Sin
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
China