Sulindac sulfone is a metabolite of sulindac, a non-steroidal anti-inflammatory drug (NSAID), without anti-inflammatory ability. VDAC1 and VDAC2 (voltage-dependent anion channel) are direct targets of sulindac sulfone which suppresses the mTORC1 pathway and induces G1 arrest[1]. At 100 microMol of sulindac sulfone, a decrease in beta-catenin concentration of 5% was observed; increasing concentrations of sulindac sulfone resulted in >70% reduction in secreted beta-catenin. Sulindac sulfone reduced levels of secreted beta-catenin in the HNSCC (head and neck squamous cell carcinoma) cell line UM-SCC 11A after 48 hours of incubation[2]. Sulindac sulfone inhibited COX-2 (cyclooxygenase) protein expression, which resulted in a decrease in prostaglandin synthase E2 production[3]. Sulindac (20 mg/kg/day), sulindac sulfone (40 mg/kg/day), or vehicle was administered orally to male Sprague-Dawley rats for a 4-wk period beginning 20 wk after tumor induction. Sulindac and sulindac sulfone treatment significantly reduced the number and volume of colorectal tumors compared with control rats[4].
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