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.
Chen
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The Hormel Institute, University of Minnesota, Austin 55912, USA.
Ma
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Dong
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D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018053:Arsenites / Q000037:antagonists & inhibitors* / Q000633:toxicity; D001241:Aspirin / Q000494:pharmacology*; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity; D002460:Cell Line; D004347:Drug Interactions; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012459:Salicylates / Q000494:pharmacology; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012878:Skin Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D018808:Transcription Factor AP-1 / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D018053:Arsenites; D002273:Carcinogens; D012459:Salicylates; D018808:Transcription Factor AP-1; D020928:Mitogen-Activated Protein Kinases; C015001:arsenite; D001241:Aspirin