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首页> 外文期刊>Biochemical Pharmacology >Selective killing of cancer cells by peptide-targeted delivery of an anti-microbial peptide
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Selective killing of cancer cells by peptide-targeted delivery of an anti-microbial peptide

机译：通过肽靶向的抗微生物肽的选择性杀伤癌细胞

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摘要

Antimicrobial peptides selectively kill bacteria while maintaining low mammalian cell cytotoxicity. However, they become cytotoxic subsequent to internalization. Here we have conjugated the lytic peptide (KLAKLAK) 2 to either a cancer-cell binding peptide (LTVSPWY) selected from peptide libraries or to a gastrin-releasing peptide (GNHWAVGHLM) in order to direct the lytic peptide to cancer cells. Peptide cytotoxicity was tested in breast MCF-7 and MDA-MB-231 cancer cells. The fusion peptides were internalized by cancer cells, disintegrated the cell membrane and induced rapid killing of the cells with IC50 values as low as 4-7 μM. Peptide cytotoxicity was dependent on the targeting receptor. Indeed, addition of free targeting peptide reduced cell killing. Blood lymphocytes and normal human mammary epithelial cells were less sensitive to the fusion peptides. Although most of the cells were killed by necrosis, fusion peptides branched with DNA oligonucleotides induced apoptosis as assayed by annexin V staining and activation of caspase 3. Therefore, the new designed drug peptides might provide a potent and selective anticancer therapy.
机译：抗菌肽选择性杀死细菌，同时保持低哺乳动物细胞的细胞毒性。但是，它们在内在化后变得具有细胞毒性。在这里，我们将裂解肽（KLAKLAK）2偶联至选自肽文库的癌细胞结合肽（LTVSPWY）或胃泌素释放肽（GNHWAVGHLM），以将裂解肽引导至癌细胞。在乳腺癌MCF-7和MDA-MB-231癌细胞中测试了肽的细胞毒性。融合肽被癌细胞内化，分解细胞膜并诱导细胞的快速杀伤，IC50值低至4-7μM。肽的细胞毒性取决于靶向受体。实际上，添加游离的靶向肽减少了细胞杀伤。血淋巴细胞和正常人乳腺上皮细胞对融合肽不那么敏感。尽管大多数细胞被坏死杀死，但通过膜联蛋白V染色和半胱天冬酶3的活化检测，融合有DNA寡核苷酸的分支肽诱导了细胞凋亡。因此，新设计的药物肽可能会提供有效的选择性抗癌治疗。

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