Schematic diagram showing proposed interplay between PAs and apoptosis-regulating proteins in p53-wild type NB cells. AdoMetDC is a key enzyme necessary for the production of dcAdoMet, a precursor in PA biosynthesis. Inhibition of AdoMetDC by SAM486A leads to the accumulation of Put as early as 8 hours after treatment. Remarkably, within the same time period, a rapid increase of native p53 protein levels was observed, suggesting that Put may be linked to p53-mediated apoptosis in these NB cells. The observed apoptosis-inducing properties of the clinically-tested SAM486A may be most effective in the treatment of NB patients with p53-wild type status, independent of their MYCN amplification status.