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Engineering of Human Lactoferrin for Improved Anticancer Activity
ACS Pharmacology & Translational Science ( IF 4.9 ) Pub Date : 2021-07-19 , DOI: 10.1021/acsptsci.1c00134
Yu Pan 1 , Niying Chua 2 , Kaisheng Lim 1 , Chun Loong Ho 1
Affiliation  

Protease-digested lactoferrin fragments often exhibit improved therapeutic properties. However, there are limited studies investigating the anticancer properties of these fragments. The fragment with improved anticancer activities is an attractive alternative to chemotherapeutic drugs—presenting severe side effects. Herein, we report the isolation and characterization of recombinant engineered-lactoferrin (rtHLF4), exhibiting up to 100-fold improved anticancer activity compared to the full-length lactoferrin (flHLF). Further, rtHLF4 exerts its anticancer effect in a shorter duration. Through transcriptomic analysis of various cancer biomarkers, rtHLF4 was found to upregulate various pro-apoptotic markers and downregulate signaling proteins involved in angiogenesis and metastasis. We further determined that rtHLF4 showed no hemolytic activity at high concentrations. We believe that this anticancer protein can be further developed as a cancer treatment.

中文翻译:

提高抗癌活性的人乳铁蛋白工程

蛋白酶消化的乳铁蛋白片段通常表现出改善的治疗特性。然而,研究这些片段的抗癌特性的研究有限。具有改善的抗癌活性的片段是化疗药物的有吸引力的替代品 - 呈现出严重的副作用。在此,我们报告了重组工程乳铁蛋白 (rtHLF4) 的分离和表征,与全长乳铁蛋白 (flHLF) 相比,其抗癌活性提高了 100 倍。此外,rtHLF4 在更短的时间内发挥其抗癌作用。通过对各种癌症生物标志物的转录组分析,发现 rtHLF4 可上调各种促凋亡标志物并下调参与血管生成和转移的信号蛋白。我们进一步确定 rtHLF4 在高浓度下没有显示溶血活性。我们相信这种抗癌蛋白可以进一步发展为癌症治疗。
更新日期:2021-07-19
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