Effects of HOXA9 Inhibitor DB818 on the Growth of Acute Myeloid Leukaemia Cells.
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Apoptosis Regulatory Proteins
/ genetics
Cell Proliferation
/ drug effects
Gene Expression Regulation, Leukemic
Homeodomain Proteins
/ antagonists & inhibitors
Humans
Leukemia, Myeloid, Acute
/ drug therapy
Proto-Oncogene Mas
Signal Transduction
THP-1 Cells
HOXA9
gene knockdown
inhibitor
leukaemia
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
28
12
2020
revised:
01
03
2021
accepted:
04
03
2021
entrez:
4
4
2021
pubmed:
5
4
2021
medline:
14
4
2021
Statut:
ppublish
Résumé
Homeobox A9 (HOXA9), a transcription factor regulating haematopoiesis and leukaemia cell proliferation, is suggested as a driver of acute myeloid leukaemia (AML). The aim of this study was to examine the effects of a synthetic HOXA9 inhibitor DB818 on AML cells in vitro. AML cell lines OCI/AML3, MV4-11, and THP-1 with gene mutations up-regulating HOXA9 expression were treated with DB818 and analysed for cell proliferation and gene expression. The effects of HOXA9 knockdown were also evaluated. In the three AML cell lines, DB818 suppressed growth, induced apoptosis, and down-regulated the expression of HOXA9 transcriptional target genes: MYB proto-oncogene, transcription factor (MYB), MYC proto-oncogene, bHLH transcription factor (MYC), and BCL2 apoptosis regulator (BCL2), while up-regulating that of Fos proto-oncogene, AP-1 transcription factor subunit (FOS). HOXA9 knockdown showed similar effects, except for MYC expression, which differed between DB818-treated and HOXA9-deficient OCI/AML3 cells, suggesting an off-target effect of DB818. DB818 has potential as a novel molecular targeted drug for treating AML associated with HOXA9 overexpression.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Homeobox A9 (HOXA9), a transcription factor regulating haematopoiesis and leukaemia cell proliferation, is suggested as a driver of acute myeloid leukaemia (AML). The aim of this study was to examine the effects of a synthetic HOXA9 inhibitor DB818 on AML cells in vitro.
MATERIALS AND METHODS
METHODS
AML cell lines OCI/AML3, MV4-11, and THP-1 with gene mutations up-regulating HOXA9 expression were treated with DB818 and analysed for cell proliferation and gene expression. The effects of HOXA9 knockdown were also evaluated.
RESULTS
RESULTS
In the three AML cell lines, DB818 suppressed growth, induced apoptosis, and down-regulated the expression of HOXA9 transcriptional target genes: MYB proto-oncogene, transcription factor (MYB), MYC proto-oncogene, bHLH transcription factor (MYC), and BCL2 apoptosis regulator (BCL2), while up-regulating that of Fos proto-oncogene, AP-1 transcription factor subunit (FOS). HOXA9 knockdown showed similar effects, except for MYC expression, which differed between DB818-treated and HOXA9-deficient OCI/AML3 cells, suggesting an off-target effect of DB818.
CONCLUSION
CONCLUSIONS
DB818 has potential as a novel molecular targeted drug for treating AML associated with HOXA9 overexpression.
Identifiants
pubmed: 33813389
pii: 41/4/1841
doi: 10.21873/anticanres.14950
doi:
Substances chimiques
Antineoplastic Agents
0
Apoptosis Regulatory Proteins
0
Homeodomain Proteins
0
MAS1 protein, human
0
Proto-Oncogene Mas
0
homeobox protein HOXA9
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1841-1847Informations de copyright
Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.