The yin and yang of nitric oxide in cancer progression

Nitric oxide (NO) is a short-lived, pleiotropic molecule that affects numerous critical functions in the body. Presently, there are markedly conflicting findings in the literature regarding NO and its role in carcinogenesis and tumor progression. NO has been shown to have dichotomous effects on cellular proliferation, apoptosis, migration, invasion, angiogenesis and many other important processes in cancer biology. It has been shown to be both pro- and antitumorigenic, depending on the concentration and the tumor microenvironment in question. NO is generated by three isoforms of NO synthase (NOS) that are widely expressed and sometimes upregulated in human tumors. Due to its vast array of physiological functions, it presents a huge challenge to researchers to discover its true potential in cancer biology and consequently, its use in anticancer therapies. In this study, we review the current knowledge in this area, with an emphasis placed on NO modulation as an anticancer therapy, focusing on NO-donating drugs and NOS inhibitors.