Sulindac

Sulindac and its metabolites sulindac sulfide and sulindac sulfone can also inhibit the NF-kappaB pathway in both colon cancer and other cell lines, due to sulindac-mediated decreases in IKKbeta kinase activity. ^[1] Sulindac sulfide significantly reduces cell number in both preconfluent and confluent cultures of HT-29 cells with the sulfide showing approximately 4-fold greater potency. Sulindac sulfide inhibits the growth of a variety of tumor cell lines derived from other tissues, as well as normal epithelial cells and fibroblasts. ^[2] Sulindac sulphide abrogates beta-catenin/TCF-mediated transcription in the CRC cell lines DLD1 and SW480, and decreases the levels of nonphosphorylated beta-catenin. ^[3]

Sulindac not only inhibits tumor formation but decreases small bowel Cox-2 and prostaglandin E(2) to baseline and restored normal levels of apoptosis in a murine modelof familial adenomatous polyposis. ^[4] Sulindac reduces the tumor number by 95% but does not alter the levels of PGE2 and LTB4 in intestinal tissues in Min/+爉ice. Sulindac reduces tumor number by 82%, whereas eicosanoid levels remained elevates in Min/+ mice. ^[5] Sulindac causes regression of 70-80% of small intestinal tumors in Min/+ mice within 4 days, but does not have the same impact on colonic lesions. ^[6]