Inhibition of arsenite-induced apoptosis by aspirin.

Arsenite exposure and subsequent arsenite-induced toxicity and carcinogenesis are common in many countries. Thus the study of chemopreventive compounds that inhibit arsenite-induced toxicity and carcinogenesis is very valuable. In the present work, we investigated the effect of aspirin on arsenite-induced apoptosis and signal transduction by means of luciferase activity, apoptosis analysis and Western blotting. Arsenite induced AP-1 transcriptional activity at the same concentration (20 microM) as was effective for inducing apoptosis. Arsenite-induced apoptosis and AP-1 transactivation in JB6 cells were blocked by aspirin and salicylate (SA). Both aspirin and SA inhibited arsenite-induced phosphorylation of Erks, but had no effect on phosphorylation of JNKs. SA inhibited arsenite-induced phosphorylation of p38 kinase, but aspirin did not. These results indicate that aspirin and SA inhibit arsenite-induced apoptosis through the inhibition of the Erks/AP-1 pathway.