Dual modes of antitumor action of an amphiphilic peptide A9K

protein
Hai Xu, Cui Xia Chen, Jing Hua, Peng Zhou, Ping Zeng, Chang Hai Cao, Jian Ren Lu

Biomaterials, 34, 2731-2737 (2013)

Following our recent report of attractive antibacterial properties of a designed amphiphilic peptide, A9K, 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 A9K penetrated HeLa cell membranes and disrupted membrane structures, a feature broadly similar to that observed from its bactericidal actions. Further interactions of A9K 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 A9K 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.

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Written by Jian Lu
<p><strong>University of Manchester, Manchester, UK</strong></p> <p>Experimental studies of biological-material interfacial processes focusing on unravelling the molecular basis of surface biocompatibility.<a href="https://softmat.net/t2t_products/lu/">-></a></p>
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