NO-Donating NSAIDs, PPAR, and Cancer: Does PPAR Contribute to Colon Carcinogenesis?
Figure 1
Effect of NO-ASA on PPARδ and other signaling
pathways. NO-ASA consists of
a traditional ASA molecule (shaded), the spacer, and –ONO2, which
releases NO, with the molecule being considered responsible for much of its
pharmacological properties. There are three positional isomers of NO-ASA (ortho, meta, and para), depending
on the position of –ONO2 in the benzene ring with respect to the
ester bond linking the ASA and spacer moieties. NO-ASA affects several cell
signaling pathways, all relevant to carcinogenesis. The modulation of these
often cross-talking pathways culminates in a net inhibitory effect on cell
growth, one of the crucial determinants of the fate of a tumor. It is likely
that such mechanistic pleiotropism by NO-ASA is central to its efficacy against
cancer.
