Sirtuin 1 Activation Suppresses the Growth of T-lymphoblastic Leukemia Cells by Inhibiting NOTCH and NF-κB Pathways.

Abstract:

BACKGROUND/AIM:The deacetylase sirtuin1 (SIRT1) inhibits tumor suppressor p53 and may promote tumorigenesis; however, SIRT1 effects on leukemia cells are controversial. The aim of this study was to clarify the activity of SIRT1 in leukemia cells. MATERIALS AND METHODS:The effects of SIRT1 inhibition or activation and SIRT1 knockdown or overexpression were examined in two T cell acute lymphoblastic leukemia (T-ALL) cell lines carrying NOTCH1 mutations and three acute myeloid leukemia (AML) cell lines. RESULTS:The growth of T-ALL cells was promoted by SIRT1 inhibition and SIRT1 knockdown but was reduced by SIRT1 activation and overexpression; however, no effects were observed in AML cells. SIRT1 activation decreased NOTCH, NF-κB, and mTOR signaling and inhibited p53, suggesting that the possible mechanisms of T-ALL growth suppression by SIRT1 are independent of p53. CONCLUSION:SIRT1 activators acting through the down-regulation of NOTCH, NF-κB, and mTOR pathways can be novel targeted drugs for NOTCH1-mutated T-ALLs.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Okasha SM,Itoh M,Tohda S

doi

10.21873/anticanres.14297

subject

Has Abstract

pub_date

2020-06-01 00:00:00

pages

3155-3161

issue

6

eissn

0250-7005

issn

1791-7530

pii

40/6/3155

journal_volume

40

pub_type

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