生物活性

• 描述Sulindac is a non-steroidal antiinflammatory agent, acts as a COX-2 inhibitor, and inhibits overexpression of COX-2. Treatment with sulindac not only inhibited tumor formation but decreased small bowel Cox-2 and prostaglandin E(2) to baseline and restored normal levels of apoptosis^[3]. Sulindac (0.1 mM to 0.5 mM) causes limited death in both p53 wt and p53 null HCT116 cells, but in combination with vitamin C, it dramatically increases almost 5-fold in cell death in p53 wt HCT116 cells relative to the vitamin C alone, and such an effect is involving caspase activation and p53 function in these cells, and via ROS-mediated pathway. Sulindac combined with vitamin C significantly increases PUMA levels, but shows no effect on Bim, Bcl-2 and Mcl-1 levels^[4]. Moreover, celecoxib and sulindac can inhibit TGF-β1-induced EMT (epithelial-mesenchymal transition) and suppress lung cancer cell migration and invasion via downregulation of SIRT1(class III deacetylase sirtuin 1) ^[5]. Sulindac can protect normal astrocytes against oxidative stress. Sulindac induces differentiation of both NSC ( neural stem cells) and GSC (glioblastoma stem cells) cells and sulindac upregulates neurogenesis in NSC. The differentiated NSC are also protected from oxidative stress damage, whereas the differentiation of GSC by sulindac increases the sensitivity of these cells to agents that cause oxidative stress^[6].