Nitric Oxide: Perspectives and Emerging Studies of a Well Known Cytotoxin

Abstract

The free radical nitric oxide (NO●) is known to play a dual role in human physiology and pathophysiology. At low levels, NO● can protect cells; however, at higher levels, NO● is a known cytotoxin, having been implicated in tumor angiogenesis and progression. While the majority of research devoted to understanding the role of NO● in cancer has to date been tissue-specific, we herein review underlying commonalities of NO● which may well exist among tumors arising from a variety of different sites. We also discuss the role of NO● in human physiology and pathophysiology, including the very important relationship between NO● and the glutathione-transferases, a class of protective enzymes involved in cellular protection. The emerging role of NO● in three main areas of epigenetics—DNA methylation, microRNAs, and histone modifications—is then discussed. Finally, we describe the recent development of a model cell line system in which human tumor cell lines were adapted to high NO● (HNO) levels. We anticipate that these HNO cell lines will serve as a useful tool in the ongoing efforts to better understand the role of NO● in cancer.

Keywords

• nitric oxide
• epigenetics
• cytotoxicity
• high NO adaptation
• oncogenetic