Mechanism of action of the synthetic imidazole compound YM 534 on human promyelocytic leukemia line HL-60 cells

Anticancer Drug Des. 1989 Aug;4(2):137-44.

Abstract

The effects of a novel anti-cancer drug, YM 534 on human promyelocytic leukemia line HL-60 cells were investigated. The growth of the cells was completely inhibited with an IC50 of 2.5 X 10(-6) M. The incorporation of 3H-thymidine or 3H-uridine into acid insoluble fraction of the cells was completely inhibited at a 10(-4) M concentration of the drug. However, that of 3H-leucine was suppressed by only 32% at this drug concentration. The single strand scission of DNA of the cells as revealed by alkali sucrose density gradient centrifugation was induced by YM 534 at a 10(-4)M concentration for 60 min. When PM2 DNA in a cell-free system was examined in the presence or absence of reducing agent, no damage to DNA was observed at a 10(-4)M YM 534. The processing of preribosomal to ribosomal RNA of HL-60 cells was retarded at a 10(-5) M level of the drug.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Line
  • DNA Damage
  • DNA, Neoplasm / drug effects
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Humans
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use*
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / metabolism
  • RNA Precursors / drug effects
  • RNA Precursors / metabolism
  • RNA Processing, Post-Transcriptional / drug effects
  • RNA, Neoplasm / drug effects
  • RNA, Neoplasm / metabolism
  • RNA, Ribosomal / drug effects
  • RNA, Ribosomal / metabolism
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • DNA, Neoplasm
  • Imidazoles
  • RNA Precursors
  • RNA, Neoplasm
  • RNA, Ribosomal