The Proapoptotic Effect of Traditional and Novel Nonsteroidal Anti-Inflammatory Drugs in Mammalian and Yeast Cells

Figure 2

The major proapoptotic pathways induced by NSAIDs. Both traditional and modified NSAIDs have been shown to induce apoptosis in eukaryotic cells by initiating mechanisms which are largely independent of COX inhibition (shown in blue), with the exception being the COX-2-dependent accumulation of arachidonic acid and subsequent synthesis of ceramide induced by sulindac and indomethacin (shown in green). Important COX-independent proapoptotic pathways induced by NSAIDs include caspase activation and modulation of Bcl-2 proteins, depletion of polyamines, modulation of NF-κB signalling and of MAP kinase activity, inhibition of Wnt/β-catenin signalling, inhibition of proteasomal function, depletion of survivin, increased expression of mda7/IL24 and also oxidative stress associated with mitochondrial dysfunction, ROS accumulation and the disruption of cellular redox balance.