Nitric oxide: perspectives and emerging studies of a well known cytotoxin.
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.
Paradise
William A
WA
Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, Chicago, IL 60612, USA; E-Mails: paradise@uic.edu (W.A.P.); vesperbe@uic.edu (B.J.V.).
Vesper
Benjamin J
BJ
Goel
Ajay
A
Waltonen
Joshua D
JD
Altman
Kenneth W
KW
Haines
G Kenneth
GK
Radosevich
James A
JA
D000818:Animals; D003603:Cytotoxins / Q000378:metabolism / Q000494:pharmacology; D044127:Epigenesis, Genetic; D051549:Glutathione S-Transferase pi / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D026361:Reactive Nitrogen Species / Q000378:metabolism
D003603:Cytotoxins; D026361:Reactive Nitrogen Species; D009569:Nitric Oxide; D051549:Glutathione S-Transferase pi