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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.[1] Sulindac sulfide is a metabolite of sulindac that has diverse activities.[2],[3] It inhibits both COX-1 and COX-2 (IC50s = 1.9 and 1.21 µM, respectively), whereas the parent compound, sulindac, is much less effective (IC50 = 58 µM for COX-2 and > 100 µM for COX-1).[4] Sulindac sulfide also inhibits aldose reductase (IC50 = 279 nM), blocking NADPH-dependent reduction of glucose to sorbitol, and reducing type 2 diabetic complications.[5] It increases the expression and activity of NAD(P)H quinone oxidoreductase [1].[6] Sulindac sulfide inhibits colorectal cancer growth both in vitro and in vivo.[7]

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