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iNOS-selective inhibitors for cancer prevention: promise and progress

Naveena B Janakiram1, Chinthalapally V Rao

  • 1Center for Cancer Prevention & Drug Development, Medical Oncology, Department of Medicine, PCS Oklahoma Cancer Center, University of Oklahoma Health Sciences, Oklahoma City, OK 73104, USA.

Future Medicinal Chemistry
|November 30, 2012
PubMed

Insights

Nitric oxide (NO) plays a dual role in cancer. While often promoting tumor growth via inducible nitric oxide synthase (iNOS), it can also induce apoptosis and regression, depending on concentration and signaling pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Nitric oxide (NO) is implicated in diverse physiological processes, with its role in tumorigenesis extensively researched.
  • Tumor progression is frequently linked to NO produced by inducible nitric oxide synthase (iNOS), often stimulated by inflammatory cytokines.
  • Conversely, NO can also trigger apoptosis and tumor regression, highlighting a complex, concentration-dependent effect.

Purpose of the Study:

  • To review the expression and generation of NO via iNOS in cancer.
  • To explore how NO modulates various signaling pathways through chemical modifications.
  • To discuss iNOS inhibitors for cancer prevention and treatment.

Main Methods:

  • Literature review of iNOS expression and NO generation in tumors.
  • Analysis of NO's impact on cellular signaling pathways and protein modifications (S-nitrosothiols, nitrosotyrosine).
  • Examination of iNOS inhibitors and their therapeutic potential in various cancers.

Main Results:

  • NO exhibits a dichotomous role in cancer, promoting progression or inducing regression based on cellular context and concentration.
  • iNOS is a key source of tumor-promoting NO, influenced by inflammatory signals.
  • NO's effects are mediated through complex signaling alterations and protein chemical modifications.

Conclusions:

  • Understanding NO's dual role and concentration-dependent effects is crucial for cancer therapy.
  • iNOS inhibitors represent a promising strategy for preventing and treating cancers, including colon cancer.
  • Targeting iNOS offers a potential therapeutic avenue by modulating NO levels in the tumor microenvironment.

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