title: The cell penetrating ability of the proapoptotic peptide, KLAKLAKKLAKLAK fused to the N-terminal protein transduction domain of translationally controlled tumor protein, MIIYRDLISH.
abstract: We show here, that the proapoptotic peptide, KLAKLAKKLAKLAK (KLA), which by itself does not penetrate cell membranes, can do so when fused to a protein transduction domain derived from NH(2)-terminus of translationally controlled tumor protein (TCTP-PTD, MIIYRDLISH). Once inside the cell, the conjugated KLA exerts its proapoptotic activity to inhibit tumor growth. We evaluated the cellular uptake of KLA fused to TCTP-PTD (hereafter called TCTP-KLA) and its effect on cancer cell viability. The IC(50) of TCTP-KLA was between 7 and 10 μmol/L. We also evaluated its anti-tumor activity in vivo by injecting it into xenografts of lung carcinoma in Balb/c nude mice. Tumor growth inhibition resulting from treatment with TCTP-KLA was better than that of TAT-KLA. These results suggest that TCTP-KLA can be applied to design cancer therapeutics.
authors.affiliation: College of Pharmacy, Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Seoul, Republic of Korea.
authors.forename: Hyo Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Seunghoo
authors.initials: S
authors.lastname: Kim
authors.forename: Hyewon
authors.initials: H
authors.lastname: Youn
authors.forename: June-Key
authors.initials: JK
authors.lastname: Chung
authors.forename: Dong Hae
authors.initials: DH
authors.lastname: Shin
authors.forename: Kyunglim
authors.initials: K
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology / Q000628:therapy; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014183:Transplantation, Heterologous; D000090324:Tumor Protein, Translationally-Controlled 1; D023041:Xenograft Model Antitumor Assays
chemical_list: D057846:Cell-Penetrating Peptides; D009363:Neoplasm Proteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; C000715647:TPT1 protein, human; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1