Aspirin inhibits colon cancer cell and tumor growth and downregulates specificity protein (Sp) transcription factors.

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Pathi S, Jutooru I, Chadalapaka G, Nair V, Lee SO, Safe S

Aspirin inhibits colon cancer cell and tumor growth and downregulates specificity protein (Sp) transcription factors.

PLoS One. 2012;7(10):e48208. doi: 10.1371/journal.pone.0048208. Epub 2012 Oct 26.

PubMed ID

23110215 [ View in PubMed

]

Abstract

Acetylsalicylic acid (aspirin) is highly effective for treating colon cancer patients postdiagnosis; however, the mechanisms of action of aspirin in colon cancer are not well defined. Aspirin and its major metabolite sodium salicylate induced apoptosis and decreased colon cancer cell growth and the sodium salt of aspirin also inhibited tumor growth in an athymic nude mouse xenograft model. Colon cancer cell growth inhibition was accompanied by downregulation of Sp1, Sp3 and Sp4 proteins and decreased expression of Sp-regulated gene products including bcl-2, survivin, VEGF, VEGFR1, cyclin D1, c-MET and p65 (NFkappaB). Moreover, we also showed by RNA interference that beta-catenin, an important target of aspirin in some studies, is an Sp-regulated gene. Aspirin induced nuclear caspase-dependent cleavage of Sp1, Sp3 and Sp4 proteins and this response was related to sequestration of zinc ions since addition of zinc sulfate blocked aspirin-mediated apoptosis and repression of Sp proteins. The results demonstrate an important underlying mechanism of action of aspirin as an anticancer agent and, based on the rapid metabolism of aspirin to salicylate in humans and the high salicylate/aspirin ratios in serum, it is likely that the anticancer activity of aspirin is also due to the salicylate metabolite.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Acetylsalicylic acid	Caspase-1	Protein	Humans	Unknown	Inhibitor Downregulator	Details
Acetylsalicylic acid	Caspase-3	Protein	Humans	Unknown	Inhibitor Downregulator	Details