New NSAID Targets and Derivatives for Colorectal Cancer Chemoprevention

  • Heather N. Tinsley
  • William E. Grizzle
  • Ashraf Abadi
  • Adam Keeton
  • Bing Zhu
  • Yaguang Xi
  • Gary A. Piazza
Chapter
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 191)

Abstract

Clinical and preclinical studies provide strong evidence that nonsteroidal anti-inflammatory drugs (NSAIDs) can prevent numerous types of cancers, especially colorectal cancer. Unfortunately, the depletion of physiologically important prostaglandins due to cyclooxygenase (COX) inhibition results in potentially fatal toxicities that preclude the long-term use of NSAIDs for cancer chemoprevention. While studies have shown an involvement of COX-2 in colorectal tumorigenesis, other studies suggest that a COX-independent target may be at least partially responsible for the antineoplastic activity of NSAIDs. For example, certain NSAID derivatives have been identified that do not inhibit COX-2 but have demonstrated efficacy to suppress carcinogenesis with potential for reduced toxicity. A number of alternative targets have also been reported to account for the tumor cell growth inhibitory activity of NSAIDs, including the inhibition of cyclic guanosine monophosphate phosphodiesterases (cGMP PDEs), generation of reactive oxygen species (ROS), the suppression of the apoptosis inhibitor protein, survivin, and others. Here, we review several promising mechanisms that are being targeted to develop safer and more efficacious NSAID derivatives for colon cancer chemoprevention.

Keywords

Familial Adenomatous Polyposis Inhibit Tumor Cell Growth Colon Tumor Cell Carboxylic Acid Moiety Colon Tumorigenesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

Funding provided by NIH grants R01 CA131378 and R01 CA148817 and a UAB Breast Cancer SPORE grant.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Heather N. Tinsley
    • 1
  • William E. Grizzle
    • 2
  • Ashraf Abadi
    • 3
  • Adam Keeton
    • 4
  • Bing Zhu
    • 4
  • Yaguang Xi
    • 4
  • Gary A. Piazza
    • 4
  1. 1.Department of Biology, Chemistry, and MathematicsUniversity of MontevalloMontevalloUSA
  2. 2.Department of PathologyThe University of Alabama at BirminghamBirminghamUSA
  3. 3.Faculty of Pharmacy and BiotechnologyGerman University of CairoCairoEgypt
  4. 4.Drug Discovery Research Center Mitchell Cancer InstituteUniversity of South AlabamaMobileUSA

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