Sulindac is a non-steroidal anti-inflammatory drug that has an extensive epidemiology documenting reduced human colorectal cancer. In mouse models, sulindac was found not only to inhibit the enzymatic activity of polyp-associated COX-2, but also to downregulate the expression of colonic COX-2 protein to control levels. Sulindac sulfone is an oxidized metabolite of sulindac that is produced in many mammals but minimally in mice and rats. It is generally considered to be inactive against COX enzymes, although it can reduce azoxymethane-induced colon cancer in rats. Sulindac sulfone inhibits aldose reductase (IC50 = 367 nM) in vitro and may contribute to the beneficial pharmacological effects of sulindac on type 2 diabetic complications.
