RRC ID 77828
Author Takenobu T, Tomizawa K, Matsushita M, Li ST, Moriwaki A, Lu YF, Matsui H.
Title Development of p53 protein transduction therapy using membrane-permeable peptides and the application to oral cancer cells.
Journal Mol Cancer Ther
Abstract 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.
Volume 1(12)
Pages 1043-9
Published 2002-10-1
PMID 12481427
MeSH Active Transport, Cell Nucleus Adenoviridae / genetics Antineoplastic Agents / pharmacology Apoptosis Blotting, Western Cell Division Cell Membrane / metabolism Cell Nucleus / metabolism Cell Survival Cisplatin / pharmacology Cyclin-Dependent Kinase Inhibitor p21 Cyclins / metabolism Gene Transfer Techniques* Genes, Reporter Genetic Vectors Humans Immunohistochemistry Microscopy, Fluorescence Mouth Neoplasms / genetics* Mouth Neoplasms / metabolism Mouth Neoplasms / therapy* Peptides / chemistry Plasmids / metabolism Protein Structure, Tertiary Recombinant Fusion Proteins / metabolism Time Factors Tumor Suppressor Protein p53 / chemistry Tumor Suppressor Protein p53 / metabolism*
IF 5.615
Human and Animal Cells Saos-2(RCB0428)