Enalapril-induced apoptosis of acute promyelocytic leukaemia cells involves STAT5A

Anticancer Res. 2012 Jul;32(7):2885-93.

Abstract

Background: In this study, we aimed at evaluating the cytotoxic and apoptotic effects of enalapril on human HL60 acute promyelocytic leukaemia cells and at clarifying the roles of signal transducers and activator of transcription proteins (STATs) on enalapril-induced cell death.

Materials and methods: Cell viability and cytotoxicity tests were conducted by Trypan blue dye exclusion and 2,3-Bis[2-methoxy-4-nitro-5-sulphophenyl]-2H-tetrazolium-5-carboxanilide inner salt (XTT) assays, respectively. Apoptotic analyses were performed by the AnnexinV-enhanced green fluorescent protein (EGFP) staining method and by fluorescence microscopy. Expression levels of STAT3, -5A and -5B genes were analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR).

Results: The results showed that enalapril reduced viability and proliferation, and induced apoptosis in HL60 cells in a dose- and time-dependent manner as compared to untreated controls. The expression levels of STAT5A gene were significantly reduced in enalapril-treated HL60 cells as compared to untreated controls.

Conclusion: Taken together, all data showed for the first time that enalapril has significant anticancer potential for the treatment of acute premyelocytic leukaemia.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Apoptosis / drug effects*
  • Dose-Response Relationship, Drug
  • Enalapril / pharmacology*
  • Gene Expression / drug effects
  • HL-60 Cells
  • Humans
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / genetics
  • Leukemia, Promyelocytic, Acute / metabolism
  • Leukemia, Promyelocytic, Acute / pathology
  • STAT3 Transcription Factor / biosynthesis
  • STAT3 Transcription Factor / genetics
  • STAT5 Transcription Factor / biosynthesis*
  • STAT5 Transcription Factor / genetics
  • Tumor Suppressor Proteins / biosynthesis*
  • Tumor Suppressor Proteins / genetics

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • STAT5 Transcription Factor
  • STAT5A protein, human
  • STAT5B protein, human
  • Tumor Suppressor Proteins
  • Enalapril