N6-isopentenyladenosine a new potential anti-angiogenic compound that targets human microvascular endothelial cells in vitro

Nucleosides Nucleotides Nucleic Acids. 2018;37(10):533-545. doi: 10.1080/15257770.2018.1503673. Epub 2018 Nov 22.

Abstract

N6-isopentenyladenosine is an anti-proliferative and pro-apoptotic atypical nucleoside for normal and tumor cells. Considering the role of angiogenesis in various diseases, we investigated the cytotoxic effect of N6-isopentenyladenosine on human microvascular endothelial cells, protagonists in angiogenesis. Our results show that N6-isopentenyladenosine induced a significant reduction of cell viability, upregulated p21 and promoted caspase-3 cleavage in a dose dependent manner leading to apoptotic cell death as detected by FACS analysis. To understand structure-function relationship of N6-isopentenyladenosine, we investigated the effect of some N6-isopentenyladenosine analogs. Our results suggest that N6-isopentenyladenosine and some of its derivatives are potentially novel angiostatic agents and might be associated with other anti-angiogenic compounds for a better outcome.

Keywords: HMEC; N6-isopentenyladenosine; angiogenesis.

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cell Cycle Checkpoints / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical / methods
  • Endothelial Cells / drug effects
  • Endothelium, Vascular / cytology*
  • Humans
  • Interferon-gamma / pharmacology
  • Isopentenyladenosine / administration & dosage
  • Isopentenyladenosine / pharmacology*

Substances

  • Angiogenesis Inhibitors
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Isopentenyladenosine
  • Interferon-gamma
  • CASP3 protein, human
  • Caspase 3