Nitric oxide (NO) is a free radical with signaling capac‑ity that plays an important role in the cardiovascular, neuronal, and immune systems, among others. NO regulates a number of physiological processes through the activation of two major signaling pathways: The activation of the en‑zyme guanylyl cyclase to form cGMP and S‑nitrosylation, a covalent attachment of an NO moiety to a reactive cys‑teine residue in peptides and proteins. NO produced by the endothelial isoform of NO synthase (eNOS) regulates blood pressure. NO produced in neurons by the neuronal NOS isoform (nNOS) functions as a neurotransmitter. The constitutively expressed isoforms eNOS and nNOS release low fluxes of NO that are associated with cell protection and proliferation. Inflammatory cytokines and toxins induce the inducible NOS isoform (iNOS) in macrophages. Production of NO under these conditions is much higher compared to its production by constitutive enzymes.[1] Higher NO fluxes such as those produced by iNOS stimulated by inflamma‑tory cytokines in macrophages or generated by millimolar concentrations of NO donors are cytotoxic and promote apoptosis.[2]

The constitutive NOS isoforms have been detected in some malignant tumors. Activation of eNOS is involved in the initiation and maintenance of tumor growth in pancreatic cancer cell lines.[3] Tumor progression in prostate cancer is associated with eNOS expression, while malignant mela‑noma progression is associated with nNOS expression.[4, 5] The iNOS isoform is ubiquitously distributed in malignant tumors, but its role in tumor development is highly complex and poorly understood.[6] The expression levels of iNOS and