Sulindac sulfone

Sulindac sulfone is an orally active metabolite of Sulindac (HY-B0008). Sulindac sulfone activates PPARγ and drives transcriptional induction of SSAT by binding to the PPRE-2 element. Sulindac sulfone induces Apoptosis. Sulindac sulfone negatively regulates the function of VDAC1/2 to inhibit the mTORC1 pathway, reduces Cyclin D1 levels, and induces G₁ cell cycle arrest in colon cancer cells. Sulindac sulfone exerts colon cancer preventive effects through a COX-independent mechanism. Sulindac sulfone can be used in research related to colon cancer^[1][2][3]. In Vitro:Sulindac sulfone (50-600 μM; 1-6 days) inhibits the proliferation and induces the death of colon cancer cell line Caco-2. After 6 days of treatment, the inhibitory effect on proliferation at concentrations ≥50 μM and the inducing effect on cell death at concentrations ≥150 μM are both statistically significant^[1].
Sulindac sulfone (600 μM; duration leading to 50% reduction in colony formation) upregulates the expression of the SSAT gene by 3.94-fold in the colon cancer cell line Caco-2 at its IC₅₀ concentration^[1].
Sulindac sulfone (10-600 μM; 24-48 h) induces the expression of SSAT mRNA in the colon cancer cell line Caco-2; at the concentration of 600 μM, the expression level increases by 2.23-fold after 24 h of treatment and by 5.58-fold after 48 h of treatment; statistically significant induction is also observed at concentrations ≥100 μM with 48 h of treatment^[1].
Sulindac sulfone (600 μM; 48 h) increases SSAT enzyme activity by 2-fold and reduces intracellular spermine and spermidine levels by 2-fold in human colon cancer Caco-2 cells^[1].
Sulindac sulfone (600 μM; 48 h) activates PPAR response elements and increases luciferase activity by 2-fold in Caco-2 colon cancer cells after 48 h of treatment^[1].
Sulindac sulfone (up to 10 mM) does not inhibit cyclooxygenase (type I) activity^[2].
Sulindac sulfone (1-100 μM) weakly inhibits 5-lipoxygenase activity, with inhibition rates of 10%, 14% and 30% at concentrations of 1 μM, 10 μM and 100 μM, respectively^[2].
Sulindac sulfone (1-100 μM) exerts no significant inhibitory effect on 15-lipoxygenase activity: the inhibition rate is 8% at 1 μM, 0% at 10 μM, while the enzyme activity increases by 15% instead at 100 μM^[2].
Sulindac sulfone (9.4-600 μM; 72 h) inhibits the growth of colon cancer HT-29, DLD-1 and SW480 cells in a dose-dependent manner. A significant reduction in cell viability is observed at concentrations ≥37.5 μM after 72 h of treatment^[3]. In Vivo:Sulindac sulfone (500-2000 ppm; dietary; continuous; 31 weeks) inhibits azoxymethane-induced colon carcinogenesis in male F344 rats in vivo in a dose-dependent manner, with the 2000 ppm dose reducing overall colon neoplasia incidence to 26.7% and total tumor multiplicity to 0.43 tumors/animal, without significantly reducing colonic PGE₂ levels^[2].