Role of cofilin1 in arsenic trioxideinduced apoptosis of NB4R1 cells.
Mol Med Rep
; 22(6): 4645-4654, 2020 Dec.
Article
em En
| MEDLINE
| ID: mdl-33174611
ABSTRACT
Alltrans retinoic acid (ATRA) and arsenic trioxide (As2O3) are currently firstline treatments for acute promyelocytic leukemia (APL). However, a number of patients with APL are resistant to ATRA but still sensitive to As2O3, and the underlying mechanisms of this remain unclear. In the present study, twodimensional gel electrophoresis, mass spectrometry and other proteomic methods were applied to screen and identify the differentially expressed proteins between the retinoic acidsensitive cell lines and drugresistant cell lines. The results demonstrated that in retinoic acidresistant NB4R1 cells, the protein expression of cofilin1 was markedly increased compared with that in the drugsensitive NB4 cells. Subsequently, the effects of cofilin1 on As2O3induced apoptosis in NB4R1 cells were further investigated. The results revealed that cell viability was markedly suppressed and apoptosis was increased in the As2O3treated NB4R1 cells, with increased expression levels of cleavedpoly (ADPribose) polymerase and cleavedcaspase 12. Cofilin1 expression was significantly decreased at both the mRNA and protein levels in the As2O3treated group compared with the control. Western blotting further revealed that As2O3 treatment decreased the cytoplasmic cofilin1 level but increased its expression in the mitochondrion. However, the opposite effects of As2O3 on the cytochrome C distribution were found in NB4R1 cells. This suggested that As2O3 can induce the transfer of cofilin1 from the cytoplasm to mitochondria and trigger the release of mitochondrial cytochrome C in NB4R1 cells. Moreover, cofilin1 knockdown by its specific short hairpin RNA significantly suppressed As2O3induced NB4R1 cell apoptosis and inhibited the release of mitochondrial cytochrome C. Whereas, overexpression of cofilin1 using a plasmid vector carrying cofilin1 increased the release of cytochrome C into the cytoplasm from the mitochondria in As2O3treated NB4R1 cells. In conclusion, cofilin1 played a role in As2O3induced NB4R1 cell apoptosis and it might be a novel target for APL treatment.
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Base de dados:
MEDLINE
Assunto principal:
Leucemia Promielocítica Aguda
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Resistencia a Medicamentos Antineoplásicos
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Cofilina 1
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article