Fig. 4

Overview of unique mechanisms of PDT-induced apoptosis on multidrug resistant cells. Light activation directly damages drug efflux pumps (P-gp and BCRP) involved in classical drug resistance and release PS into the cytosol which localizes on mitochondria and lysosome. Upon activation, damages the antiapoptotic BCL-2 family proteins and lysosomal membrane. The Lyso-PDT induces the proteolytic activity that cleaves BID to tBID and leads to mitochondria pore opening via BAX action. The pore opening caused the release of cytochrome c and SMAC (second mitochondrion-derived activator of caspases) from the intermembrane mitochondrion space. The SMAC promotes caspase activation by binding with IAPs (inhibitor of apoptosis protein) and cytochrome c forms complex which leads to cell death through caspase action. Membrane damage after PDT leads to depolarization, reduction of active transport and lipid peroxidation which help in activation of death signal and thus cell death