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In vitro activities of native and designed peptide antibiotics against drug sensitive and resistant tumor cell lines

Cited 81 time in Web of Science Cited 84 time in Scopus
Authors
Kim, Sunkyu; Kim, Sukwon; Bang, Yung-Jue; Kim, Seong-Jin; Lee, Byeong Jae
Issue Date
2003-07
Citation
Peptides, Vol.24 No.7, pp.945-953
Keywords
MDRantimicrobial peptidegaegurin 6derivativeantitumor activityMCF-7/DOX
Abstract
In order to develop peptide agents with reduced length and enhanced tumoricidal activity, we have designed gaegurin 6 (GGN6) derivatives through deletions and/or substitutions of amino acids. The deletion of hydrophobic amino terminal region completely abolished antitumor activity whereas the deletion of carboxy terminal region had little influence on antitumor activity. Antitumor activity of the PTP peptides did not correlate with antibacterial activity. PTP7, the most potent derivative, was found to have comparable antitumor activity to GGN6 in spite of reduced number of amino acids which is about half the size of gaegurin 6; furthermore, it showed little cytotoxicity on PBMCs and RBCs. GGN6 and PTP7 also showed equivalent cytotoxicity against drug sensitive (MCF-7) and multidrug-resistant cell lines (MCF-7/DOX). Plasma membrane blebbing and DNA fragmentation of peptide-treated tumor cells indicated that the peptides could induce apoptosis in tumor cells. These results suggest that GGN6 and its derivatives can be developed as new anticancer agents and may provide a new strategy for overcoming MDR which is a major problem in cancer therapy. (C) 2003 Elsevier Inc. All rights reserved.
ISSN
0196-9781
URI
https://hdl.handle.net/10371/173242
DOI
https://doi.org/10.1016/S0196-9781(03)00194-3
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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