Cell penetrating peptide TAT can kill cancer cells via membrane disruption after attachment of camptothecin
Cell penetrating peptide TAT can kill cancer cells via membrane disruption after attachment of camptothecin
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细胞穿透肽 TAT 在附着喜树碱后可以通过膜破裂来杀死癌细胞。
DOI：
10.1016/j.peptides.2014.12.001
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发表时间：
2015-01-01
期刊：
影响因子：
3
通讯作者：
Wang, Rui
中科院分区：
文献类型：
--
作者：
Song, Jingjing;Zhang, Yun;Wang, Rui
将传统抗癌药物与细胞穿透肽连接是提高其在癌症治疗中应用的有效策略。在本研究中，我们通过将喜树碱（CPT）连接到细胞穿透肽达特的N端，设计并合成了TAT-CPT和达特-2CPT偶联物。有趣的是，我们发现TAT-CPT，特别是达特-2CPT可以通过膜破坏杀死癌细胞，这与抗菌肽相似。这可能是因为CPT可以作为疏水残基，以增加达特的膜插入程度和孔的稳定性。此外，TAT-CPT和达特-2CPT进入细胞后释放出的CPT也能杀伤癌细胞。因此，CPT的加入可以使穿膜肽达特成为具有双重抗癌作用的抗菌肽，为开发基于穿膜肽的抗癌肽提供了新的思路。(C)2014爱思唯尔公司All rights reserved.
Attachment of traditional anticancer drugs to cell penetrating peptides is an effective strategy to improve their application in cancer treatment. In this study, we designed and synthesized the conjugates TAT-CPT and TAT-2CPT by attaching camptothecin (CPT) to the N-terminus of the cell penetrating peptide TAT. Interestingly, we found that TAT-CPT and especially TAT-2CPT could kill cancer cells via membrane disruption, which is similar to antimicrobial peptides. This might be because that CPT could perform as a hydrophobic residue to increase the extent of membrane insertion of TAT and the stability of the pores. In addition, TAT-CPT and TAT-2CPT could also kill cancer cells by the released CPT after they entered cells. Taken together, attachment of CPT could turn cell penetrating peptide TAT into an antimicrobial peptide with a dual mechanism of anticancer action, which presents a new strategy to develop anticancer peptides based on cell penetrating peptides. (C) 2014 Elsevier Inc. All rights reserved.