Figure 1, Key Figure. Pleotropic effects of nitric oxide in cancer.

NO and NOS activate anti-oncogenic pathways that can suppress tumor progression in certain types of cancers by activating p53 or suppressing epigenetic modifications (green panel). NO donors diethylenetriamine NONOate (deta-NONOate), S-Nitroso-N-Acetyl-D,L-Penicillamine (SNAP), and S-Nitrosoglutathiones (R-GSNO) provide exogenous NO to activate or amplify tumor-suppressing effects.

NO synthesis and NOS expression promote tumorigenic properties via induction of metabolic hypoxia, aberrant S-nitrosation, irregular epigenetic modifications, increased inflammation, exploiting p53 mutations and reprogramming TME metabolism (red panel). NO synthesis or NOS is targeted for anticancer treatment using NOS inhibitors L-N^G-Nitroarginine methyl ester (L-NAME), L-N^G-Nitroarginine (L-NNA), or arginine depletion drug, L-asparaginase. Key intermediate pathways induced by NO or NOS are proposed as co-targets for combination therapy to improve therapeutic efficacy.