Anticancer Actions of Azurin and Its Derived Peptide p28

Cancers are a great threat to humans. In cancer therapy, surgical removal of the tumor combined with radiotherapy and chemotherapy is the most routine treatment procedure and usually the most effective. However, radiotherapy and chemotherapy drugs that kill cancer cells efficiently also kill normal cells, thus exhibiting large side effects. Cancer-targeted drugs, which aim to specifically recognize proteins or signaling pathways associated with tumor proliferation and migration, have achieved marked progress in recent years. Azurin is a copper-containing redox protein secreted by Pseudomonas aeruginosa. Azurin and its derived peptide p28 preferentially enter a variety of cancer cells and induce apoptosis or cell cycle arrest. Mechanistic studies revealed that azurin and p28 target the p53 and receptor tyrosine kinase signaling pathways as well as other pathways. Two phase I trials of p28 have been carried out, with findings that p28 is safe and exhibits anticancer activity in both adult and pediatric patients. In this review paper, we provide an up-to-date summary of progress on the anticancer mechanisms and therapeutic strategies for azurin and p28.