Identification of a novel cell-penetrating peptide targeting human glioblastoma cell lines as a cancer-homing transporter
| Autor: | Chitoshi Takayama, Eisaku Kondo, Mariko Nakamura, Tomoyuki Tsumuraya, Masanori Sunagawa, Chigusa Shimizu-Okabe, Shogo Ishiuchi, Chiaki Katagiri, Masayuki Matsushita, Moritoshi Higa |
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| Rok vydání: | 2014 |
| Předmět: |
Cell type
media_common.quotation_subject Molecular Sequence Data Biophysics Antineoplastic Agents Cell-Penetrating Peptides Biology Biochemistry Cell Line Tumor mRNA display Humans Amino Acid Sequence Internalization Molecular Biology media_common Brain Neoplasms Retinoblastoma protein Membrane Transport Proteins Cell Biology Molecular biology Apoptosis Cell culture Cell-penetrating peptide biology.protein Cancer research Glioblastoma Homing (hematopoietic) |
| Zdroj: | Biochemical and biophysical research communications. 457(2) |
| ISSN: | 1090-2104 |
| Popis: | 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 p16INK4a 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. |
| Databáze: | OpenAIRE |
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