Is inducible nitric oxide synthase a target for chemoprevention?
The molecular messenger nitric oxide (NO) is synthesized endogenously from L-arginine by three isoforms of the enzyme NO synthase. The isoform most consistently associated with neoplasia is the inducible form, inducible nitric oxide synthase (iNOS). However, the role played by the NO/iNOS system in tumor development is complex, and both promoting and inhibitory effects on neoplasia have been reported. This review attempts to clarify the role of iNOS in carcinogenesis, with particular emphasis on the early stages of tumor development, offers possible explanations for the confused picture presented in the literature regarding the association of the NO/iNOS pathway with neoplasia, and identifies selective iNOS inhibitors that may have chemopreventive potential.
Crowell
James A
JA
National Cancer Institute, Division of Cancer Prevention, Chemopreventive Agent Development Research Group, Bethesda, Maryland 20892, USA. jcrowell@mail.nih.gov
Steele
Vernon E
VE
Sigman
Caroline C
CC
Fay
Judith R
JR
D000818:Animals; D018890:Chemoprevention; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II
D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II