Molecular and Cellular Biochemistry

, Volume 283, Issue 1–2, pp 159–167 | Cite as

tNOX, an alternative target to COX-2 to explain the anticancer activities of non-steroidal anti-inflammatory drugs (NSAIDS)

  • D. James Morré
  • Dorothy M. Morre


Our work has identified a cancer-specific, cell surface and growth-related quinol oxidase with both NADH oxidase and protein disulfide-thiol interchange activities, a member of the ECTO-NOX protein family designated tNOX. We provide evidence for tNOX as an alternative drug target to COX-2 to explain the anticancer activity of COX inhibitors. Non-steroidal anti-inflammatory drugs (NSAIDS), piroxicam, aspirin, ibuprofen, naproxen and celecoxib all specifically inhibited tNOX activity of HeLa (human cervical carcinoma) and BT-20 (human mammary carcinoma) cells (IC50 in the nanomolar range) without effect on ECTO-NOX activities of non-cancer MCF-10A mammary epithelial cells. With cancer cells, rofecoxib was less effective and two NSAIDS selective for COX-1 were without effect in inhibiting NOX activity. The IC50 for inhibition of tNOX activity of HeLa cells and the IC50 for inhibition of growth of HeLa cells in culture were closely correlated. The findings provide evidence for a new drug target to account for anticancer effects of NSAIDS that occur independent of COX-2.


aspirin cancer celecoxib cyclooxygenase ECTO-NOX hydroquinone (NADH) oxidase: tNOX NADH oxidase non-steroidal anti-inflammatory drugs (NSAIDS) rofecoxib tumor associated hydroquinone (NADH) oxidase 


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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Department of Medicinal Chemistry and Molecular PharmacologyPurdue UniversityWest LafayetteUSA
  2. 2.Department of Foods and NutritionPurdue UniversityWest LafayetteUSA
  3. 3.Department of Medicinal Chemistry and Molecular PharmacologyPurdue UniversityWest LafayetteUSA

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