Cell penetrating peptide TAT can kill cancer cells via membrane disruption after attachment of camptothecin |
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| Institution: | 1. Molecular Biology Laboratory, Scuola Normale Superiore, Area della Ricerca del CNR, Via Moruzzi 1, 56100 Pisa, Italy;2. Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Padriciano 99, 34149 Trieste, Italy;3. Centre for Integrative Biology (CIBIO), University of Trento, Via delle Regole 101, 38123 Trento, Italy;4. Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy;1. Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran;2. Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran;3. Department of Pharmaceutical Nanotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran;4. Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran;5. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran;6. Department of Medical Nanotechnology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran;7. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran |
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| Abstract: | Attachment of traditional anticancer drugs to cell penetrating peptides is an effective strategy to improve their application in cancer treatment. In this study, we designed and synthesized the conjugates TAT-CPT and TAT-2CPT by attaching camptothecin (CPT) to the N-terminus of the cell penetrating peptide TAT. Interestingly, we found that TAT-CPT and especially TAT-2CPT could kill cancer cells via membrane disruption, which is similar to antimicrobial peptides. This might be because that CPT could perform as a hydrophobic residue to increase the extent of membrane insertion of TAT and the stability of the pores. In addition, TAT-CPT and TAT-2CPT could also kill cancer cells by the released CPT after they entered cells. Taken together, attachment of CPT could turn cell penetrating peptide TAT into an antimicrobial peptide with a dual mechanism of anticancer action, which presents a new strategy to develop anticancer peptides based on cell penetrating peptides. |
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| Keywords: | Cell penetrating peptide Antimicrobial peptide Anticancer activity Camptothecin Membrane disruption |
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