Recognizing that the concentration range of 8-bromo-cAMP and 8-bromo-cGMP used in the activation experiments far exceed physiological concentrations of intracellular cAMP (0.53 ± 0.03 pmol per μg protein) and cGMP (0.21 ± 0.01 pmol per μg protein) measured in NSCLC cell lines treated with PDE inhibitors, we next evaluated whether increased intracellular cyclic purine nucleotides can modulate the phosphorylation of both PKA and PKG targets under physiological conditions (Figure S5). This evidence concerns the gene PRKG1 and non-small cell lung carcinoma.