Arias Mauricio, Hilchie Ashley L, Haney Evan F, Bolscher Jan G M, Hyndman M Eric, Hancock Robert E W, Vogel Hans J
a Biochemistry Research Group, Department of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada.
b Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
Biochem Cell Biol. 2017 Feb;95(1):91-98. doi: 10.1139/bcb-2016-0175. Epub 2016 Nov 3.
Lactoferrin (LF) is a mammalian host defense glycoprotein with diverse biological activities. Peptides derived from the cationic region of LF possess cytotoxic activity against cancer cells in vitro and in vivo. Bovine lactoferricin (LFcinB), a peptide derived from bovine LF (bLF), exhibits broad-spectrum anticancer activity, while a similar peptide derived from human LF (hLF) is not as active. In this work, several peptides derived from the N-terminal regions of bLF and hLF were studied for their anticancer activities against leukemia and breast-cancer cells, as well as normal peripheral blood mononuclear cells. The cyclized LFcinB-CLICK peptide, which possesses a stable triazole linkage, showed improved anticancer activity, while short peptides hLF11 and bLF10 were not cytotoxic to cancer cells. Interestingly, hLF11 can act as a cell-penetrating peptide; when combined with the antimicrobial core sequence of LFcinB (RRWQWR) through either a Pro or Gly-Gly linker, toxicity to Jurkat cells increased. Together, our work extends the library of LF-derived peptides tested for anticancer activity, and identified new chimeric peptides with high cytotoxicity towards cancerous cells. Additionally, these results support the notion that short cell-penetrating peptides and antimicrobial peptides can be combined to create new adducts with increased potency.
乳铁蛋白（LF）是一种具有多种生物活性的哺乳动物宿主防御糖蛋白。从LF阳离子区域衍生的肽在体外和体内对癌细胞具有细胞毒性活性。牛乳铁蛋白肽（LFcinB）是一种源自牛LF（bLF）的肽，具有广谱抗癌活性，而源自人LF（hLF）的类似肽活性则较低。在这项研究中，研究了几种源自bLF和hLF N端区域的肽对白血病和乳腺癌细胞以及正常外周血单核细胞的抗癌活性。具有稳定三唑键的环化LFcinB-CLICK肽显示出增强的抗癌活性，而短肽hLF11和bLF10对癌细胞没有细胞毒性。有趣的是，hLF11可以作为一种细胞穿透肽；当通过Pro或Gly-Gly接头与LFcinB的抗菌核心序列（RRWQWR）结合时，对Jurkat细胞的毒性增加。总之，我们的工作扩展了用于测试抗癌活性的LF衍生肽库，并鉴定了对癌细胞具有高细胞毒性的新型嵌合肽。此外，这些结果支持了短细胞穿透肽和抗菌肽可以结合以产生具有更高效力的新加合物的观点。
