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.
Highlights
Nitric oxide (NO) is a molecule with a very short half-life, produced by the action of nitric oxide synthases
The discovery of multiple NO-mediated pathways within cancer has unlocked a number of novel NO-based therapies. Many of these novel therapies center around delivery of NO directly to the tumor and tumor microenvironment (TME)
Such localized increases in NO may reverse chemotherapeutic and radiotherapeutic resistance mediated by hypoxia-inducible factor1α (HIF-1α), preclinical trials have suggested the efficacy with a number of other mechanisms
Summary
Nitric oxide (NO) is a molecule with a very short half-life, produced by the action of nitric oxide synthases. As the body of scientific literature grew, the role of nitric oxide within carcinogenesis has been more clearly defined. For those seeking to make therapeutics, nitric oxide appears to have the capability to be both tumor-promoting and tumoricidal. Determining which effect predominates is complex and often depends upon the tissue NO exerts its effects, the concentration of NO administered, and tumor microenvironment. These discoveries have led to a wide number of proposed uses for NO as an anticancer agent, either alone or in combination with other treatment modalities [4]. We discuss the impact of NO in cancer therapy and outline its role as an emerging anticancer agent
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