Description
Sulindac sulfone (59864-04-9) is a metabolite of the cyclooxygenase inhibitor sulindac that induces apoptosis via inhibition of type 5 phosphodiesterases.1 Sulindac sulfone does not inhibit cyclooxygenase at physiological concentrations but does inhibit K-ras-dependent cyclooxygenase-2 expression in colon cancer cells.2 Modulates beta-catenin mediated effects. 3
Uses
Sulindac Sulfone is an inhibitor of growth and inducer of apoptosis in cancer cell lines.
Biochem/physiol Actions
Sulindac sulfone is non-steroidal anti-inflammatory drug and an analgesic that has antiproliferative and apoptotic effects. It inhibits the expression and activity of cyclooxygenase-2 in human colon cancer cells1,2 and reduces tumor burden in adenomatous polyposis patients.3
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[1]. 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 [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].
References
References/Citations
1) Thompson et al. (2000) Exisulind induction of apoptosis involves guanosine 3′,5′-cyclic monophosphate phosphodiesterase inhibition, protein kinase G activation and attenuated beta-catenin. Cancer Res., 60 3338
2) Taylor et al. (2000) Sulindac sulfone inhibits K-ras-dependent cyclooxygenase-2 expression in human colon cancer cells; Cancer Res. 60 6607
3) Bravi et al. (2015) Sulindac metabolites decrease cerebrovascular malformations in CCM-3 knockout mice; Proc. Natl. Acad. Sci. USA 112 8421
