Current Advances of Nitric Oxide in Cancer and Anticancer Therapeutics

Abstract

Nitric oxide (NO) is a short-lived, ubiquitous signaling molecule that affects numerous critical functions in the body. There are markedly conflicting findings in the literature regarding the bimodal effects of NO in carcinogenesis and tumor progression, which has important consequences for treatment. Several preclinical and clinical studies have suggested that both pro- and antitumorigenic effects of NO depend on multiple aspects, including, but not limited to, tissue of generation, the level of production, the oxidative/reductive (redox) environment in which this radical is generated, the presence or absence of NO transduction elements, and the tumor microenvironment. Generally, there are four major categories of NO-based anticancer therapies: NO donors, phosphodiesterase inhibitors (PDE-i), soluble guanylyl cyclase (sGC) activators, and immunomodulators. Of these, NO donors are well studied, well characterized, and also the most promising. In this study, we review the current knowledge in this area, with an emphasis placed on the role of NO as an anticancer therapy and dysregulated molecular interactions during the evolution of cancer, highlighting the strategies that may aid in the targeting of cancer.

Counteracting Action of Curcumin on High Glucose-Induced Chemoresistance in Hepatic Carcinoma Cells

“…The enhanced level of nitric oxide was observed in curcumin treated groups, both in NG or HG medium. Both pro-and antitumor effects of nitric oxide level are reported (41), which are largely affected by factors including type of tissue, concentration level, cell sensitivity, tumor microenvironment, and hypoxia/re-oxygenation level (41,42). In liver cancer, elevated level of nitric oxide is linked with growth arrest and apoptosis along with chemosensitization through modulated levels of p53 and HIF-1a (42).…”

The Etiology and Pathophysiology Genesis of Benign Prostatic Hyperplasia and Prostate Cancer: A New Perspective

“…Nitric oxide serves many biological functions [302][303][304]; ageing is frequently associated with l-arginine deficiency [305,306] and with the menopausal transition in women [307], as a substrate for nitric oxide synthase. Both oral l-citrulline and/or l-arginine supplementation increases nitric oxide bioavailability levels in plasma and tissue [241][242][243][244][245]308].…”

New azolyl-derivatives as multitargeting agents against breast cancer and fungal infections: synthesis, biological evaluation and docking study

“…Since compounds 2-8 and 13-20 bear azole moieties potentially able to inhibit the iNOS 16 and considering the involvement of this enzyme in breast cancer progression 20 , we evaluated them as iNOS inhibitors, with the aim to ascertain their potential dualaction. The L-citrulline assay with fluorimetric detection was adopted, as previously reported 21 .…”

“…In particular, 13a chemical scaffold was modified connecting to the stereogenic centre a benzyl group instead of the phenyl one, and different bulky aromatic moieties by means of an ester, or urethane, or a thiourethane group (Figure 1, compounds 2-8). Compound 3o was modified by introducing a triazole instead of the imidazole as the aromatase haem-coordinating moiety, and inserting different substituents on the aromatic ring, similarly to the previously reported imidazolyl-piperidine sulphonamides (Figure 1, compounds [13][14][15][16][17][18][19][20]. Considering the therapeutic diversity of many azole-based compounds 13,14 and the multifactorial features of BC, it was supposed that molecules 2-8 and 13-20 could be useful to manage such a pathological condition acting as multi-target-directed ligands.…”