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Is inducible nitric oxide synthase a target for chemoprevention?
James A Crowell1, Vernon E Steele, Caroline C Sigman
1National Cancer Institute, Division of Cancer Prevention, Chemopreventive Agent Development Research Group, Bethesda, Maryland 20892, USA. jcrowell@mail.nih.gov
Abstract:
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.
Insights
The inducible nitric oxide synthase (iNOS) enzyme
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Nitric oxide (NO) is synthesized from L-arginine by NO synthase (NOS) enzymes.
- Inducible NOS (iNOS) is linked to neoplasia, but its role in tumor development is complex and debated.
- Both tumor-promoting and tumor-inhibiting effects of the NO/iNOS system have been reported.
Purpose of the Study:
- To clarify the role of iNOS in carcinogenesis, focusing on early tumor development.
- To explain conflicting reports on the NO/iNOS pathway's association with neoplasia.
- To identify selective iNOS inhibitors with potential chemopreventive applications.
Main Methods:
- Literature review and synthesis of existing research on iNOS and cancer.
- Analysis of studies investigating the dual role of NO/iNOS in tumor initiation and progression.
- Evaluation of potential therapeutic strategies targeting iNOS.
Main Results:
- The NO/iNOS system exhibits context-dependent effects in carcinogenesis.
- Early-stage carcinogenesis may be influenced differently by iNOS compared to later stages.
- Selective iNOS inhibition shows promise for cancer chemoprevention.
Conclusions:
- The role of iNOS in cancer is complex, with stage-specific effects.
- Understanding these complexities is crucial for developing targeted cancer therapies.
- Selective iNOS inhibitors represent a potential avenue for cancer chemoprevention.
