Dual modes of antitumor action of an amphiphilic peptide A(9)K.
Dual modes of antitumor action of an amphiphilic peptide A(9)K.
复制标题
两亲肽 A(9)K 的双重抗肿瘤作用模式。
DOI：
10.1016/j.biomaterials.2012.12.039
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发表时间：
2013-04
期刊：
影响因子：
14
通讯作者：
Lu, Jian Ren
中科院分区：
文献类型：
--
作者：
Xu, Hai;Chen, Cui Xia;Hu, Jing;Zhou, Peng;Zeng, Ping;Cao, Chang Hai;Lu, Jian Ren
在我们最近报道了一种设计的两亲性多肽A9K具有诱人的抗菌特性后，我们通过检测其对不同类型哺乳动物细胞的作用方式来研究其抗肿瘤活性。该多肽对HeLa癌细胞和人早幼粒白血病HL60细胞的生长有强烈的抑制作用，而对宿主细胞包括CoS 7细胞、小鼠成纤维细胞NIH3T3细胞和人红细胞则保持良性。扫描电子显微镜和荧光显微镜的图像显示，A9K穿透HeLa细胞膜并破坏膜结构，这一特征与从其杀菌作用中观察到的特征大致相似。A9K与细胞内膜的进一步相互作用导致线粒体功能障碍，与F-肌动蛋白重组和bcl2和c-myc基因转录减少有关，导致HeLa细胞在线粒体诱导的凋亡途径中发生凋亡。因此，A9K对肿瘤细胞具有很高的选择性，并通过膜破裂和细胞凋亡两种作用模式杀死它们。此外，该多肽不会引起非特异性免疫效应，也不会被蛋白酶降解。这些特征对于开发它们在未来研究中的应用至关重要。
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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DOI：
10.1007/bf01870697
发表时间：
2005
期刊：
The Journal of Membrane Biology
影响因子：
--
作者：
M. Tosteson;S. Holmes;M. Razin;D. Tosteson
通讯作者：
M. Tosteson;S. Holmes;M. Razin;D. Tosteson
影响因子：
23.4
作者：
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通讯作者：
Stoeckle, Michael
影响因子：
4.8
作者：
Papo, N;Shahar, M;Shai, Y
通讯作者：
Shai, Y
影响因子：
8
作者：
Sreenath V. Sharma
通讯作者：
Sreenath V. Sharma
影响因子：
11.2
作者：
Papo, Niv;Seger, Dalia;Shai, Yechiel
通讯作者：
Shai, Yechiel