Sulindac sulfone is a metabolite of the nonsteroidal anti-inflammatory drug sulindac. Sulindac sulfone is an inhibitor of aldose reductase (IC50 =367 nM).

Aldose reductase:367 nM

In vitro: Sulindac sulfone treatment also inhibited PGE2 production by HCA-7 cells with an IC50 of 360 mmol/L. Sulindac sulfone at 100 mmol/L reduced 6-ketoPGFα by 29.2%. Sulindac sulfone reduced the colony number of HCA-7 and HCT-116 with an EC50 of 50 mmol/l. Sulindac sulfone significantly decreased the expression of total cellular β-catenin (50% of control), pro-caspase 3 (49%), cyclin D1 (51%), and PPARδ (65%) in SW480 cells. No significant alteration in pro-caspase 3 or β-catenin expression was found in HCA7, LS174, or Caco-2 cells treated with sulindac sulfone. A dose-dependent reduction in TCF-mediated transcriptional activity was also observed in SW480 cells [1][2].

In vivo: Sulindac sulfone is capable of reducing the incidence, multiplicity, and tumor burden in the azoxymethane AOM rat model of colorectal cancer. Sulindac sulfone had no effect on the growth of HCA-7, HCT-116 xenografts, and cancer cell xenografts [1].