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Functional and structural characteristics of anticancer peptide Pep27 analogues
BACKGROUND: A secreted peptide Pep27 initiates the cell death program in S. pneumoniae through signal transduction. This study was undertaken to evaluate the relation between the structure and cytotoxic activity of Pep27 and its analogues on cancer cells. RESULTS: Pep27anal2 characterized substituti...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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BioMed Central
2005
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1199608/ https://www.ncbi.nlm.nih.gov/pubmed/16004618 http://dx.doi.org/10.1186/1475-2867-5-21 |
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author | Lee, Dong Gun Hahm, Kyung-Soo Park, Yoonkyung Kim, Hai-Young Lee, Weontae Lim, Sung-Chul Seo, Youn-Kyung Choi, Cheol-Hee |
author_facet | Lee, Dong Gun Hahm, Kyung-Soo Park, Yoonkyung Kim, Hai-Young Lee, Weontae Lim, Sung-Chul Seo, Youn-Kyung Choi, Cheol-Hee |
author_sort | Lee, Dong Gun |
collection | PubMed |
description | BACKGROUND: A secreted peptide Pep27 initiates the cell death program in S. pneumoniae through signal transduction. This study was undertaken to evaluate the relation between the structure and cytotoxic activity of Pep27 and its analogues on cancer cells. RESULTS: Pep27anal2 characterized substituting ((2)R→W), ((4)E→W), ((11)S→W) and ((13)Q→W) in native Pep27, exhibited greater hydrophobicity and anticancer activity than Pep27 and other analogues. The IC(50 )values of Pep27anal2 were approximately 10 – 30 μM in a number of cell lines (AML-2, HL-60, Jurkat, MCF-7 and SNU-601). Confocal microscopy showed that Pep27anal2-FITC was localized in the plasma membrane, and then moving from the membrane to subcellular compartments with the initiation of membrane blebbing. Flow cytometric analysis using propidium iodide and Annexin V also revealed that Pep27anal2 induced apoptosis with minor membrane damage. Electron microscopy revealed that Pep27 induced apoptosis in Jurkat cells. The anticancer activity of Pep27anal2 was neither abrogated by pan-caspase inhibitor (Z-VAD-fmk) nor related to cytochrome c release from mitochondria. The 3D solution structures of these two Pep27 peptides revealed that both form a random coil conformation in water; however, they adopted stable α-helical conformations in solutions. CONCLUSION: The results indicate that Pep27anal2 can penetrate the plasma membrane, and then induce apoptosis in both caspase-and cytochrome c-independent manner. The hydrophobicity of Pep27anal2 appears to play an important role in membrane permeabilization and/or anticancer properties. The structure-functional relationships of these peptides are also discussed. It is proposed that Pep27anal2 is a potential candidate for anticancer therapeutic agents. |
format | Text |
id | pubmed-1199608 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-11996082005-09-09 Functional and structural characteristics of anticancer peptide Pep27 analogues Lee, Dong Gun Hahm, Kyung-Soo Park, Yoonkyung Kim, Hai-Young Lee, Weontae Lim, Sung-Chul Seo, Youn-Kyung Choi, Cheol-Hee Cancer Cell Int Primary Research BACKGROUND: A secreted peptide Pep27 initiates the cell death program in S. pneumoniae through signal transduction. This study was undertaken to evaluate the relation between the structure and cytotoxic activity of Pep27 and its analogues on cancer cells. RESULTS: Pep27anal2 characterized substituting ((2)R→W), ((4)E→W), ((11)S→W) and ((13)Q→W) in native Pep27, exhibited greater hydrophobicity and anticancer activity than Pep27 and other analogues. The IC(50 )values of Pep27anal2 were approximately 10 – 30 μM in a number of cell lines (AML-2, HL-60, Jurkat, MCF-7 and SNU-601). Confocal microscopy showed that Pep27anal2-FITC was localized in the plasma membrane, and then moving from the membrane to subcellular compartments with the initiation of membrane blebbing. Flow cytometric analysis using propidium iodide and Annexin V also revealed that Pep27anal2 induced apoptosis with minor membrane damage. Electron microscopy revealed that Pep27 induced apoptosis in Jurkat cells. The anticancer activity of Pep27anal2 was neither abrogated by pan-caspase inhibitor (Z-VAD-fmk) nor related to cytochrome c release from mitochondria. The 3D solution structures of these two Pep27 peptides revealed that both form a random coil conformation in water; however, they adopted stable α-helical conformations in solutions. CONCLUSION: The results indicate that Pep27anal2 can penetrate the plasma membrane, and then induce apoptosis in both caspase-and cytochrome c-independent manner. The hydrophobicity of Pep27anal2 appears to play an important role in membrane permeabilization and/or anticancer properties. The structure-functional relationships of these peptides are also discussed. It is proposed that Pep27anal2 is a potential candidate for anticancer therapeutic agents. BioMed Central 2005-07-11 /pmc/articles/PMC1199608/ /pubmed/16004618 http://dx.doi.org/10.1186/1475-2867-5-21 Text en Copyright © 2005 Lee et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Primary Research Lee, Dong Gun Hahm, Kyung-Soo Park, Yoonkyung Kim, Hai-Young Lee, Weontae Lim, Sung-Chul Seo, Youn-Kyung Choi, Cheol-Hee Functional and structural characteristics of anticancer peptide Pep27 analogues |
title | Functional and structural characteristics of anticancer peptide Pep27 analogues |
title_full | Functional and structural characteristics of anticancer peptide Pep27 analogues |
title_fullStr | Functional and structural characteristics of anticancer peptide Pep27 analogues |
title_full_unstemmed | Functional and structural characteristics of anticancer peptide Pep27 analogues |
title_short | Functional and structural characteristics of anticancer peptide Pep27 analogues |
title_sort | functional and structural characteristics of anticancer peptide pep27 analogues |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1199608/ https://www.ncbi.nlm.nih.gov/pubmed/16004618 http://dx.doi.org/10.1186/1475-2867-5-21 |
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