The chemopreventive NO-donating NSAIDs (NO-NSAIDs; NSAIDs with an NO-releasing moiety) modulate PPARδand offer the opportunity to revisit the controversial role of PPARδin carcinogenesis (several papers report that PPARδeither promotes or inhibits cancer). This review summarizes the pharmacology of NO-NSAIDs, PPARδcancer biology, and the relationship between the two. In particular, a study of the chemopreventive effect of two isomers of NO-aspirin on intestinal neoplasia inMinmice showed that, compared to wild-type controls, PPARδis overexpressed in the intestinal mucosa ofMinmice; PPARδresponds tom- andp-NO-ASA proportionally to their antitumor effect (p->m-). This effect is accompanied by the induction of epithelial cell death, which correlates with the antineoplastic effect of NO-aspirin; and NO-aspirin's effect on PPARδis specific (no changes in PPARαor PPARγ). Although these data support the notion that PPARδpromotes intestinal carcinogenesis and its inhibition could be therapeutically useful, more work is needed before a firm conclusion is reached.
NO-Donating NSAIDs, PPARδ, and Cancer: Does PPARδContribute to Colon Carcinogenesis?
