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N itric oxide (NO) is a free radical with signaling capacity 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 enzyme guanylyl cyclase to form cGMP and S-nitrosylation, a covalent attachment of an NO moiety to a reactive cysteine 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 inflammatory 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 melanoma 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 Special EditionCancer is a worldwide health problem leading to a high incidence of morbidity and mortality. Malignant transformation can occur by expression of oncogenes, over-expression and deregulated activation of proto-oncogenes, and inactivation of tumor suppressor genes. These cellular actions occur through stimulation of oncogenic signaling pathways. Nitric oxide (NO) can induce genetic changes in cells and its intracellular generation can lead to tumor formation and progression. It can also promote anti-tumor activities. The pro-and anti-tumor activities of NO are dependent on its intracellular concentration, cell compartmentalization, and cell sensitivity. NO affects a number of oncogenic signaling pathways. This review focuses on two oncogenic signaling pathways: NO-EGFR-Src-FAK and NO-Ras-EGFR-ERK1/2 MAP kinases. In these pathways, low to intermediate concentrations of NO/S-nitrosothiols (RSNOs) stimulate oncogenic signaling, while high concentrations of NO/RSNO stimulate anti-oncogenic signaling. Increasing knowledge on pro-and anti-tumorigenic activities of NO and related reactive species such as RSNOs has fostered the research and synthesis of novel NO-based chemotherapeutic agents. RSNOs, effective as NO donors and trans-nitrosylating agents under appropriate conditions, may operate as potential chemotherapeutic agents. (Biomed J 2015;38:380-388) associat...

Nitric Oxide (NO) and Hydrogen Sulfide (H2S) are components of an “interactome”, which is defined as a redox system involving the interactions of RSS, RNS and ROS. Chemical interaction by these species is common and is characterized by one and two electron oxidation, nitrosylation, nitration and sulfuration/polysulfidation reactions. NO and H2S are gases that penetrate cell membranes, are synthesized by specific enzymes, are ubiquitous, regulate protein activities through post-translational modifications and participate in cell signaling. The two molecules at high concentrations compared to physiological concentrations may result in cellular damage particularly through their interaction with other reactive species. NO and H2S can interact with each other and form a variety of molecular species which may have constructive or destructive behavior depending on the cell type, the cellular environment (ex. oxygen tension, pH, redox state), where the products are produced and in what concentrations. Cross talk exists between NO and H2S, whereby they can influence the generation and signaling behavior of each other. Given the above mentioned properties of NO and H2S and studies in cancer cells and animal models employing NO and H2S donors that generate higher than physiological concentrations of NO and H2S and are effective in killing cancer cells but not normal cells, lend credence to the possibility of the utility of these donors in an approach to the treatment of cancer.

The stem bark of Guarea macrophylla Vahl. ssp. tuberculata Vellozo (Meliaceae) was submitted to steam distillation and adsorption chromatographic separation. Seventeen sesquiterpenes, one diterpene and four fatty acids were identified using a combination of GC, GC-MS, 1 H-and 13 C-NMR.