NO-donating aspirin inhibits the growth of leukemic Jurkat cells and modulates beta-catenin expression.
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.
Nath
Niharika
N
Department of Physiology and Pharmacology, City University of New York Medical School, New York, NY 10031, USA.
Labaze
Georges
G
Rigas
Basil
B
Kashfi
Khosrow
K
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D019169:Jurkat Cells; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D015534:Trans-Activators / Q000378:metabolism*; D051176:beta Catenin
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D020030:Nitric Oxide Donors; D015534:Trans-Activators; D051176:beta Catenin; D020169:Caspases; D001241:Aspirin