p28 Bacterial Peptide, as an Anticancer Agent

Abstract

Cancer remains a major cause of morbidity and mortality irrespective of the type of conventional chemotherapy. Therefore, there is an urgent need for new and effective anticancer therapeutic agents. Bacterial proteins and their derivative peptides appear as a promising approach for cancer treatment. Several, including an amphipathic, α-helical, 28-amino acid peptide derived from azurin, a 128-amino acid copper-containing redox protein secreted from Pseudomonas aeruginosa, show clinical promise in the treatment of adult and pediatric solid tumors. The peptide, p28, is a post-translational, multi-target anticancer agent that preferentially enters a wide variety of solid tumor cells. Mechanistically, after entry, p28 has two major avenues of action. It binds to both wild-type and mutant p53 protein, inhibiting constitutional morphogenic protein 1 (Cop1)-mediated ubiquitination and proteasomal degradation of p53. This results in increased levels of p53, which induce cell-cycle arrest at G2/M and an eventual apoptosis that results in tumor cell shrinkage and death. In addition, p28 also preferentially enters nascent endothelial cells and decreases the phosphorylation of FAK and Akt inhibiting endothelial cell motility and migration. Here, we review the current basic and clinical evidence suggesting the potential of p28 as a cancer therapeutic peptide.

Delivery of Various Cargos into Cancer Cells and Tissues via Cell-Penetrating Peptides: A Review of the Last Decade

“…Azurin is a 128 residue periplasmic bacterial blue copper protein found in Pseudomonas aeruginosa [ 104 ]. Amino acids 50–77 (p28) of azurin are fundamentally responsible for azurin’s penetration capacity into cancer cells [ 105 ]. Mehta and colleagues demonstrated the ability of p28 to penetrate into human umbilical vein endothelial cells (HUVEC), mediating the inhibition of VEGF-induced migration and inducing antiangiogenic effects in multiple xenograft models.…”

TAT for Enzyme/Protein Delivery to Restore or Destroy Cell Activity in Human Diseases

“…The peptide was able to inhibit angiogenesis and cancer cell growth [ 89 , 90 ]. In addition, p28 was found to preferentially enter tumor cells [ 91 ]. Noei and his team designed a novel therapeutic molecule, based on the fusion of p28 to Apoptin (p28-Apoptin) [ 92 ].…”

“…CPPs are commonly utilized for developing enzyme/protein-based modalities, based on their ability to deliver various large cargoes, including enzymes/proteins, into cells. However, there is still no FDA-approved CPP-protein drug, although CPP-protein molecules are currently in their first clinical trials, both for replacing the mitochondrial frataxin protein (TAT-FXN; [ 77 ]) and for destroying cells as in the case of p28 for the treatment of solid p53 tumor [ 91 ].…”

A novel chimeric protein with enhanced cytotoxic effects on breast cancer in vitro and in vivo

“…Finally, the histological examination of the samples was performed using a BHS system microscope (Olympus Corporation, Tokyo, Japan). [19][20][21][22][23][24][25][26]…”