Use of Clostridium perfringens Enterotoxin and the Enterotoxin Receptor-Binding Domain (C-CPE) for Cancer Treatment: Opportunities and Challenges

Figure 1

Model for CPE-induced cytotoxicity. CPE first binds to claudin receptors to form an ~90 kDa small complex. Six small complexes are then thought to oligomerize on the membrane surface to form a CH-1 prepore. The prepore then inserts into membranes to form the active pore. This results in entry of calcium into cells, which activates calpain. When a high CPE dose is used, there is substantial entry of calcium into cells, causing a strong calpain activation; this results in cell death by oncosis. Lower CPE doses cause more limited calcium influx and thus a milder calpain activation; these cells die by classical caspase 3-mediated apoptosis.