title: Identification of a novel cell-penetrating peptide targeting human glioblastoma cell lines as a cancer-homing transporter.
abstract: Cell-penetrating peptides (CPPs) as a novel biomedical delivery system have been highly anticipated, since they can translocate across biological membranes and are capable of transporting their cargo inside live cells with minimal invasiveness. However, non-selective internalization in various cell types remains a challenge in the clinical application of CPPs, especially in cancer treatment. In this study, we attempted to identify novel cancer-homing CPPs to target glioblastoma multiforme (GBM), which is often refractory and resistant to treatment. We screened for CPPs showing affinity for the human GBM cell line, U87MG, from an mRNA display random peptide library. One of the candidate peptides which amino-acid sequence was obtained from the screening showed selective cell-penetrating activity in U87MG cells. Conjugation of the p16(INK4a) functional peptide to the GBM-selective CPP induced cellular apoptosis and reduced phosphorylated retinoblastoma protein levels. This indicates that the CPP was capable of delivering a therapeutic molecule into U87MG cells inducing apoptosis. These results suggest that the novel CPP identified in this study permeates with high affinity into GBM cells, revealing it to be a promising imaging and therapeutic tool in the treatment of glioblastoma.
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan.
authors.forename: Moritoshi
authors.initials: M
authors.lastname: Higa
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Katagiri
authors.affiliation: Department of Molecular Anatomy, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan.
authors.forename: Chigusa
authors.initials: C
authors.lastname: Shimizu-Okabe
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Tsumuraya
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Sunagawa
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Neurosurgery, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Ishiuchi
authors.affiliation: Department of Molecular Anatomy, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan.
authors.forename: Chitoshi
authors.initials: C
authors.lastname: Takayama
authors.affiliation: Division of Molecular and Cellular Pathology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuou-ku, Niigata 951-8510, Japan.
authors.forename: Eisaku
authors.initials: E
authors.lastname: Kondo
authors.affiliation: Department of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, 903-0215 Okinawa, Japan. Electronic address: masayuki@med.u-ryukyu.ac.jp.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Matsushita
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data
chemical_list: D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; D026901:Membrane Transport Proteins
keywords: CPP; Cancer; DDS; Glioblastoma; Peptide