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

• Published in: Biomaterials 2013-04, Vol.34 (11), p.2731-2737
• Main Authors: Xu, Hai, Chen, Cui Xia, Hu, Jing, Zhou, Peng, Zeng, Ping, Cao, Chang Hai, Lu, Jian Ren
• Format: Article
• Language: English
• Subjects: Actins - genetics; Actins - metabolism; Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Cell Membrane - drug effects; Cercopithecus aethiops; Chromatography, High Pressure Liquid; COS Cells; Down-Regulation; Erythrocytes; Genes, myc - genetics; HeLa Cells; HL-60 Cells; Humans; Mice; Microscopy, Electron, Scanning; Microscopy, Fluorescence; Mitochondria - drug effects; NIH 3T3 Cells; Peptides - chemistry; Peptides - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; Surface-Active Agents - chemistry; Surface-Active Agents - pharmacology; Transcription Factors - genetics; Transcription Factors - metabolism
• ISSN: 1878-5905
• DOI: 10.1016/j.biomaterials.2012.12.039

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.