Liu Q, Zhao H, Jiang Y, Wu M, Tian Y, Wang D, Lao Y, Xu N, Li Z
School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, China; Shenzhen Key Lab of Tissue Engineering, The Second People's Hospital of Shenzhen, Shenzhen, China.
School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School , Shenzhen, China.
Cell Death Discov. 2016 Mar 7;2:16008. doi: 10.1038/cddiscovery.2016.8. eCollection 2016.
Despite great advances in cancer therapy, drug resistance is a difficult hurdle to overcome that requires development of anticancer agents with novel and effective modes of action. In a number of studies, lytic peptides have shown remarkable ability to eliminate cancer cells through a different way from traditional treatments. Lytic peptides are positively charged, amphiphilic, and are efficient at binding and disrupting the negatively charged cell membrane of cancer cells. In this study, we described the anticancer properties of a lytic peptide that was developed on the basis of the alignment of amphiphilic BH3 peptides. Our results demonstrated that the positive charge and conformation constraint were favourable for efficient cancer cell elimination. Artificial BCL-2 homology 3 peptides (ABH3) exhibited effective anticancer effects against a series of cancer cell lines in vitro and in HeLa human cervical tumour xenografts in vivo. ABH3 induced cell death in an apoptosis-independent manner through the lytic properties of the peptide that caused disruption of cell membrane. Our results showed that charge tuning and conformation constraining in a lytic peptide could be applied to optimise the anticancer activity of lytic peptides. These results also suggest that ABH3 may be a promising beginning for the development of additional lytic peptides as anticancer reagents.
尽管癌症治疗取得了巨大进展，但耐药性是一个难以克服的障碍，这需要开发具有新颖有效作用方式的抗癌药物。在许多研究中，溶细胞肽已显示出通过与传统治疗不同的方式消除癌细胞的显著能力。溶细胞肽带正电荷，具有两亲性，并且能够有效地结合并破坏癌细胞带负电荷的细胞膜。在本研究中，我们描述了一种基于两亲性BH3肽序列开发的溶细胞肽的抗癌特性。我们的结果表明，正电荷和构象限制有利于有效消除癌细胞。人工BCL-2同源3肽（ABH3）在体外对一系列癌细胞系以及在体内对HeLa人宫颈肿瘤异种移植模型均表现出有效的抗癌作用。ABH3通过其导致细胞膜破坏的溶细胞特性以非凋亡依赖的方式诱导细胞死亡。我们的结果表明，溶细胞肽中的电荷调节和构象限制可用于优化溶细胞肽的抗癌活性。这些结果还表明，ABH3可能是开发更多溶细胞肽作为抗癌试剂的一个有前景的开端。
