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Biomaterials. 2013 Apr;34(11):2731-7. doi: 10.1016/j.biomaterials.2012.12.039. Epub 2013 Jan 23.

Dual modes of antitumor action of an amphiphilic peptide A(9)K.

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  • 1State Key Laboratory of Heavy Oil Processing and the Centre for Bioengineering and Biotechnology, China University of Petroleum East China, Qingdao 266555, China. xuh@upc.edu.cn

Abstract

Following our recent report of attractive antibacterial properties of a designed amphiphilic peptide, A(9)K, we have investigated its antitumor activities by examining the modes of its action against different mammalian cell types. The peptide strongly inhibited the growth of cancerous HeLa cells and human promyelocytic leukemia HL60 cells whilst remaining benign to the host cells, including Cos 7 cells, mouse fibroblast NIH3T3 cells and human red blood cells. Images from SEM and fluorescence microscopy showed that A(9)K penetrated HeLa cell membranes and disrupted membrane structures, a feature broadly similar to that observed from its bactericidal actions. Further interactions of A(9)K with inner cellular membranes caused mitochondrial dysfunction associated with the F-actin reorganization and the decreased transcription of bcl-2 and c-myc genes, resulting in HeLa cell apoptosis in a mitochondria-induced apoptosis pathway. Thus A(9)K has high selectivity against cancerous cells and kills them by dual modes of action: membrane disruption and cell apoptosis. In addition, the peptide does not induce non-specific immunological effects and is not degraded by proteases. These features are crucial for developing their applications in future research.

Copyright © 2013 Elsevier Ltd. All rights reserved.

PMID:
23352040
[PubMed - indexed for MEDLINE]
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