Neomycin, but Not Neamine, Blocks Angiogenic Factor Induced Nitric Oxide Release through Inhibition of Akt Phosphorylation

Abstract

Angiogenesis, the growth of new blood vessels, is a critical factor of carcinogenesis. Neomycin and neamine, two drugs blocking the nuclear translocation of angiogenin (ANG), have been proven to inhibit tumour growth in vivo. However, the high toxicity of neomycin prevents its therapeutic use, thus indicating that the less toxic neamine may be a better candidate. Endothelial cells were cultured on a biocompatible multiple microelectrode array (MMA). The release of NO evoked by ANG or vascular endothelial growth factor (VEGF) was detected electrochemically. The effects of neomycin and neamine on ANG- and VEGF-induced NO releases have been investigated. Neomycin totally blocks NO release for concentrations down to the pM range, probably through the inhibition of the Akt kinase phosphorylation, as revealed by confocal microscopy. On the other hand, both ANG- and VEGF-induced NO releases were not significantly hindered by the presence of high concentrations of neamine. The inhibition of the Akt pathway and NO release are expected to lead to a severe decrease in tissue growth and repair, thus indicating a possible cause for the toxicity of neomycin. Furthermore, the data presented here show that ANG- and VEGF-induced NO releases are not dependent on the nuclear translocation of angiogenin, as these events were not abolished by the presence of neamine.