NO-donating aspirin inhibits the growth of leukemic Jurkat cells and modulates beta-catenin expression

Biochem Biophys Res Commun. 2005 Jan 7;326(1):93-9. doi: 10.1016/j.bbrc.2004.11.009.


beta-Catenin has been implicated in leukemic cell proliferation. We compared the effects of aspirin (ASA) and the ortho, meta, and para positional isomers of NO-donating aspirin (NO-ASA) on cell growth and beta-catenin expression in human Jurkat T leukemic cells. Cell growth inhibition was strong: IC(50) for p-, o-, and m- were 20+/-1.6 (mean+/-SEM), 15+/-1.5, and 200+/-12 microM, respectively, in contrast to that of ASA (3200+/-375 microM). The para isomer of NO-ASA degraded beta-catenin in a dose- and time-dependent manner coinciding with increasing expression of activated caspase-3. The caspase inhibitor ZVAD blocked beta-catenin cleavage by p-NO-ASA and partially reversed cell growth inhibition by p-NO-ASA but not that by ASA. A denitrated analog of p-NO-ASA did not degrade beta-catenin indicating the importance of the NO-donating moiety. Our findings suggest that NO-ASA merits further study as an agent against leukemia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • Antineoplastic Agents / pharmacology*
  • Aspirin / pharmacology*
  • Caspases / metabolism
  • Cell Proliferation / drug effects*
  • Cytoskeletal Proteins / metabolism*
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Jurkat Cells
  • Nitric Oxide Donors / pharmacology*
  • Trans-Activators / metabolism*
  • beta Catenin


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Nitric Oxide Donors
  • Trans-Activators
  • beta Catenin
  • Caspases
  • Aspirin