title: Trans-membrane peptide therapy for malignant glioma by use of a peptide derived from the MDM2 binding site of p53.
abstract: A new strategy is required against glioblastoma, a highly aggressive and fatal disease. In recent studies the protein transduction domains (PTDs) of some proteins, which are able to cross biological membranes, have been identified as critical domains for protein transduction. Here, we show that this protein-delivery system is a powerful tool for transduction of p53, a biologically active tumor-suppressor protein, into cancer cells, to suppress their proliferation. A 15-amino-acid sequence corresponding to the mouse double minutes clone2 (MDM2) binding site of p53 was shown by cell proliferation assay and MTT assay to have a proliferation-inhibiting effect on glioma cells. The polyarginine11R as a PTD, nuclear localization sequence (NLS), and laminin (Ln) fused to the p53 peptide corresponding to the MDM2 binding site (p53-NLS-Ln-11R) effectively penetrated the plasma membrane of the glioma cells and was translocated into the nucleus. At a 10 μM:  concentration, this peptide inhibited the proliferation of human glioma cells, whether the p53 gene had mutated or not. These results suggest that this protein-transduction method using the p53-NSL-Ln-11R peptide may become a promising glioma therapy as an alternative gene therapy.
authors.affiliation: Department of Neurosurgery, Yokohama City University School of Medicine, Yokohama, Japan. sachikopan0612@yahoo.co.jp
authors.forename: Sachiko
authors.initials: S
authors.lastname: Yamada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanno
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kawahara
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D009336:Necrosis; D010446:Peptide Fragments / Q000494:pharmacology*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D020169:Caspases