Azoxystrobin Induces Apoptosis and Cell Cycle Arrest in Human Leukemia Cells Independent of p53 Expression.
Antineoplastic Agents
/ pharmacology
Apoptosis
/ drug effects
Cell Cycle Checkpoints
/ drug effects
Cell Proliferation
/ drug effects
HL-60 Cells
Humans
Leukemia, Myeloid
/ drug therapy
Leukemia, T-Cell
/ drug therapy
Pyrimidines
/ pharmacology
Signal Transduction
Strobilurins
/ pharmacology
Tumor Suppressor Protein p53
/ metabolism
Azoxystrobin
apoptosis
cancer
p53
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Mar 2022
Mar 2022
Historique:
received:
12
01
2022
revised:
03
02
2022
accepted:
04
02
2022
entrez:
27
2
2022
pubmed:
28
2
2022
medline:
8
3
2022
Statut:
ppublish
Résumé
Azoxystrobin (AZOX), a methoxyacrylate derivative, has potent antimicrobial and antitumor activities. Here, we report the anticancer effects of AZOX on the p53-negative human myelogenous leukemia cell line HL-60RG and the p53 positive human T-cell leukemia cell line MOLT-4F. Using both leukemia cells, the anticancer effect of AZOX treatment was analyzed throughout the cell cycle. AZOX damaged both cell lines dose-dependently, and the cell damage rates were almost the same in both lines. Cell cycle distribution analysis showed that the treated MOLT-4F cells arrested at the S phase, whereas HL-60RG cells increased during the subG1 phase, suggesting that cell death was occurring. AZOX-induced cell death in HL-60RG was inhibited with the addition of uridine, which is used as a substrate for the salvage pathway of pyrimidine nucleotides. AZOX has p53-independent anticancer effects in leukemia cells, but the mechanisms underlying the damage differ between cell lines.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Azoxystrobin (AZOX), a methoxyacrylate derivative, has potent antimicrobial and antitumor activities. Here, we report the anticancer effects of AZOX on the p53-negative human myelogenous leukemia cell line HL-60RG and the p53 positive human T-cell leukemia cell line MOLT-4F.
MATERIALS AND METHODS
METHODS
Using both leukemia cells, the anticancer effect of AZOX treatment was analyzed throughout the cell cycle.
RESULTS
RESULTS
AZOX damaged both cell lines dose-dependently, and the cell damage rates were almost the same in both lines. Cell cycle distribution analysis showed that the treated MOLT-4F cells arrested at the S phase, whereas HL-60RG cells increased during the subG1 phase, suggesting that cell death was occurring. AZOX-induced cell death in HL-60RG was inhibited with the addition of uridine, which is used as a substrate for the salvage pathway of pyrimidine nucleotides.
CONCLUSION
CONCLUSIONS
AZOX has p53-independent anticancer effects in leukemia cells, but the mechanisms underlying the damage differ between cell lines.
Identifiants
pubmed: 35220221
pii: 42/3/1307
doi: 10.21873/anticanres.15598
doi:
Substances chimiques
Antineoplastic Agents
0
Pyrimidines
0
Strobilurins
0
TP53 protein, human
0
Tumor Suppressor Protein p53
0
azoxystrobin
NYH7Y08IPM
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1307-1312Informations de copyright
Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.