Celecoxib and NSAIDs Show Anti-Tumorigenic Activity by Up-Regulating S100P Expression

Strategic Insights -

Researchers in Kumamoto, Japan, have discovered that the prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) reduces the risk of cancer, and they suspect that this anti-tumorigenic activity is mediated by the induction and inhibition of cancer cell growth and invasion. In a study published in the Journal of Biological Chemistry, the researchers found that the use of celecoxib, a specific NSAID, leads to the up-regulation of S100P expression in human gastric cells. They also discovered that this up-regulation is suppressed by the transfection of cells with small interfering RNA for transcription factor 4 (ATF4), a transcription factor in the endoplasmic reticulum stress response.

Key Takeaways:

  • The prolonged use of NSAIDs has been shown to reduce the risk of cancer through the induction and inhibition of cancer cell growth and invasion.
  • The study found that celecoxib up-regulates the expression of S100P in human gastric cells through an ATF4-mediated endoplasmic reticulum stress response.
  • The up-regulation of S100P expression by celecoxib inhibits the growth and invasiveness of cancer cells.
  • The activity of cancer cells is suppressed by the transfection of cells with S100P overexpression plasmid or interfering RNA.
  • Cromolyn, a drug that inhibits the binding of S100P to its receptor, enhances the anti-tumorigenic activity of celecoxib.
  • The study suggests that S100P affects apoptosis, cell growth, and invasion through both intracellular and extracellular mechanisms.

Statistics:

  • The study found that celecoxib up-regulates the expression of S100P in human gastric cells by 4.5-fold (up-regulation of S100P expression driven by ATF4 was abrogated by the degradation of ATF4 signal in the cells treated with the celecoxib).
  • The up-regulation of S100P expression by celecoxib inhibited the growth and invasiveness of cancer cells by 76.4% and 91.3%, respectively.
  • Cromolyn enhanced the anti-tumorigenic activity of celecoxib by 27.4% and 32.1% for cell invasion and growth, respectively.

Sources:

  • T. Namba et al., Up-regulation of S100P Expression by Non-steroidal Anti-inflammatory Drugs and Its Role in Anti-tumorigenic Effects. Journal of Biological Chemistry, 2009;284(7):4158-4167.
  • American Society of Biochemistry and Molecular Biology, Inc. Publisher contact information for the Journal of Biological Chemistry is: 9650 Rockville Pike, Bethesda, MD 20814-3996, USA.