Differentiation agents increase the potential AraC therapy of AML by reactivating cell death pathways without enhancing ROS generation.
J Cell Physiol
; 235(1): 573-586, 2020 01.
Article
en En
| MEDLINE
| ID: mdl-31245853
ABSTRACT
Acute myeloid leukemia (AML) has a poor prognosis and requires new approaches for treatment. We have reported that a combination of vitamin D-based cell differentiation agents (doxercalciferol/carnosic acid [D2/CA]) added following the cytotoxic drug arabinocytosine (AraC) increases AML cell death (CD), a model for improved therapy of this disease. Because AraC-induced CD is known to involve reactive oxygen species (ROS) generation, here we investigated if the modulation of cellular REDOX status plays a role in the enhancement of cell death (ECD) by D2/CA. Using thiol antioxidants, such as N-acetyl cysteine (NAC), we found a significant inhibition of ECD, yet this occurred in the absence of any detectable change in cellular ROS levels. In contrast, NAC reduced the vitamin D receptor (VDR) abundance and its signaling of ECD. Importantly, VDR knockdown and NAC similarly inhibited ECD without producing an additive effect. Thus, the proposed post-AraC therapy may be compromised by agents that reduce VDR levels in AML blasts.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Leucemia Mieloide Aguda
/
Apoptosis
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Receptores de Calcitriol
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Citarabina
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Antimetabolitos Antineoplásicos
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
J Cell Physiol
Año:
2020
Tipo del documento:
Article