Development of p53 protein transduction therapy using membrane-permeable peptides and the application to oral cancer cells.

Recent studies suggest that several proteins can transverse biological membranes through protein transduction. The protein transduction domains of these proteins, 10-16 residues long, have been identified as critical domains for the protein transduction. Poly-arginine peptide also has the ability of protein transduction. Here, we show that the protein delivery system using 11 poly-arginine peptides (11R) is a powerful tool for the transduction of the biologically active tumor suppressor protein, p53, to suppress the proliferation of oral cancer cells. The 11R-fused p53 proteins (11R-p53) effectively penetrated across the plasma membrane of the cancer cells and translocated into the nucleus. The proteins induced the activity of the p21/WAF promoter and inhibited the proliferation of human oral cancer cells, in which the p53 gene was mutated. The effect was equivalent to that of the adenovirus-mediated p53 gene transduction system. Moreover, 11R-p53 enhanced the cisplatin-dependent induction of apoptosis of the cells. These data suggest that this protein transduction method may become a promising cancer therapy.