Nitric oxide synthases in cancer genetics; focus on nasopharyngeal carcinoma

The tumorigenesis is a complex pathophysiological process involving several inflammatory signalling and molecular mechanisms leading to the progressive cell transformation and formation of cancer. Several lines of evidence showed that inflammation is involved in cancer development and progression and chronic inflammatory diseases can promote cell transformation and tumorigenesis [1-4]. In response to endogenous and exogenous stimuli, activated inflammatory cells such as macrophages, sentinel dendritic cells, endothelial cells and neutophils are able to synthesize and release a plethora of inflammatory factors including lipid mediators, cytokines, reactive oxygen species (ROS), matrix metalloproteases, and NO [5-7]. It has been demonstrated that NO is one of the most multifunctional gaseous molecule involved in inflammation-driven diseases such as cancer [8,9]. Since its discovery and the historic Nobel Prize in Physiology and Medicine 1998 awarded to Ferid Murad, Robert Furchgott and Louis J. Ignarro, NO has sparked a lot of scientific research in all the fields of biology and medical sciences with fascinating results and an exponential number of scientific publications. Despite its short half-life, NO participates in various biological and pathological functions. NO is a very fascinating and attractive molecule in that it by itself exhibits opposite effects depending on its variable production and its heterogeneous chemistry. It has been reported that NO has pro and anti-inflammatory activities due to the biphasic regulation of NF-kB [10]. NO is distinctly known as an intracellular signaling molecule with complex and dichotomous effects. The dual role of NO in cancer biology demonstrate its dynamic involvement in tumor development and progression. In cancer, the heterogeneous effects of NO are dependent on many factors such as the activity and localization of NOS isoforms, concentration and duration of NO exposure, and cellular sensitivity to NO [11]. The well-known dual effects of NO are closely linked to its concentration which is under the control of several factors primarily genetic variations affecting its bioavailability. In carcinogenesis, it is known that at low concentrations (less than 100 nM), NO acts as a pro-tumorigenic factor [12]. However, high concentrations of NO (more than 500 nM) were known to be proapoptotic causing cytotoxic and anti-tumorigenic effects [13].