Azoxystrobin Induces Apoptosis and Cell Cycle Arrest in Human Leukemia Cells Independent of p53 Expression

Anticancer Res. 2022 Mar;42(3):1307-1312. doi: 10.21873/anticanres.15598.

Abstract

Background/aim: 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: Using both leukemia cells, the anticancer effect of AZOX treatment was analyzed throughout the cell cycle.

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: AZOX has p53-independent anticancer effects in leukemia cells, but the mechanisms underlying the damage differ between cell lines.

Keywords: Azoxystrobin; apoptosis; cancer; p53.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Cycle Checkpoints / drug effects*
  • Cell Proliferation / drug effects*
  • HL-60 Cells
  • Humans
  • Leukemia, Myeloid / drug therapy*
  • Leukemia, Myeloid / metabolism
  • Leukemia, Myeloid / pathology
  • Leukemia, T-Cell / drug therapy*
  • Leukemia, T-Cell / metabolism
  • Leukemia, T-Cell / pathology
  • Pyrimidines / pharmacology*
  • Signal Transduction
  • Strobilurins / pharmacology*
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Antineoplastic Agents
  • Pyrimidines
  • Strobilurins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • azoxystrobin