Abstract

Azurin, a member of the cupredoxin family of redox proteins, secreted by the bacterium Pseudomonas aeruginosa, preferentially penetrates human cancer cells and exerts cytostatic and cytotoxic (apoptotic) effects with no apparent activity on normal cells. Amino acids 50-77 (p28; 2.9 kDa) of azurin also preferentially penetrate cancer cells and provide a significant part of the antiproliferative activity of azurin against a variety of tumour cell lines. Although amino acids 50-67 of azurin (p18) appear as the minimal motif (protein transduction domain; PTD) responsible for azurin’s preferential entry into human cancer cells, p28, but not p18, exerts significant, dose- and time-related, cell cycle inhibitory and apoptotic effects by forming a complex with the tumour suppressor protein p53 and reducing proteasomal degradation of p53 through a non MDM2 mediated pathway(s). As a lead compound, p28 provides a new approach to develop anti-cancer therapeutics.