Vitamin C promotes anti-leukemia of DZNep in acute myeloid leukemia.
Biochim Biophys Acta Mol Basis Dis
; 1868(5): 166357, 2022 05 01.
Article
em En
| MEDLINE
| ID: mdl-35143932
ABSTRACT
The epigenetic treatment by 3-Deazaneplanocin A (DZNep), a histone methyltransferase inhibitor, shows great potential against acute myeloid leukemia (AML). However, the variant sensitivity and incomplete response to DZNep are commonly observed. Here, we reveal that vitamin C (Vc) dramatically promotes DZNep response against leukemic cells in different cell lines and primary AML samples. Vc enhances apoptosis and differentiation induced by DZNep in different AML cell lines in vitro and reduces leukemia progression in vivo. At the molecular level, Vc downregulates an enzyme of serine synthesis named D-3-phosphoglycerate dehydrogenase (PHGDH), as well as BCL2, an anti-apoptotic gene. Over-expression of PHGDH reverses the Vc-enhanced anti-leukemic effect of DZNep in AML cells. Therefore, our findings provide an effective approach to reduce the resistance against epigenetic treatment by Vc, which shows a potential improvement of their combination in AML patients.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia Mieloide Aguda
/
Proteína Potenciadora do Homólogo 2 de Zeste
Limite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta Mol Basis Dis
Ano de publicação:
2022
Tipo de documento:
Article