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Updated: Aug 18, 2025

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
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Neomycin, but Not Neamine, Blocks Angiogenic Factor Induced Nitric Oxide Release through Inhibition of Akt

Raphaël Trouillon1, Dong-Ku Kang2, Soo-Ik Chang3

  • 1Department of Bioengineering, Imperial College London, London SW7 2BP, UK.

International Journal of Molecular Sciences
|December 11, 2022
PubMed

Insights

Neomycin inhibits tumor growth by blocking angiogenin (ANG) nuclear translocation and nitric oxide (NO) release, but causes toxicity. Neamine, less toxic, does not significantly inhibit ANG- or VEGF-induced NO release, suggesting NO release is independent of ANG nuclear translocation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biomedical Engineering

Background:

  • Angiogenesis, the formation of new blood vessels, is crucial for cancer development.
  • Neomycin and neamine inhibit tumor growth by blocking angiogenin (ANG) nuclear translocation.
  • Neomycin's high toxicity limits its therapeutic application, making neamine a potential alternative.

Purpose of the Study:

  • To investigate the effects of neomycin and neamine on nitric oxide (NO) release induced by ANG and vascular endothelial growth factor (VEGF).
  • To explore the potential toxicity mechanisms of neomycin related to the Akt pathway and NO inhibition.
  • To determine if ANG- and VEGF-induced NO release is dependent on ANG nuclear translocation.

Main Methods:

  • Culturing endothelial cells on a biocompatible multiple microelectrode array (MMA).
  • Electrochemical detection of NO release evoked by ANG or VEGF.
  • Confocal microscopy to assess Akt kinase phosphorylation.

Main Results:

  • Neomycin completely inhibited NO release at pM concentrations, likely via Akt pathway inhibition.
  • Neamine did not significantly hinder ANG- or VEGF-induced NO releases, even at high concentrations.
  • ANG- and VEGF-induced NO releases were independent of ANG nuclear translocation.

Conclusions:

  • Neomycin's toxicity may stem from its inhibition of the Akt pathway and NO release, crucial for tissue repair.
  • Neamine is a less toxic alternative that does not impede NO release.
  • The study demonstrates that angiogenesis-related NO release is not dependent on angiogenin's nuclear translocation.
Keywords:
angiogenesisbio-electrochemical methodscells-on-a-chipdrug screeningnitric oxide

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