Pan Yu, Chua Niying, Lim Kaisheng, Ho Chun Loong
Department of Biomedical Engineering, Southern University of Science and Technology (SUSTech), Shenzhen, China.
School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive 637551, Jurong West, Singapore.
ACS Pharmacol Transl Sci. 2021 Jul 19;4(5):1476-1482. doi: 10.1021/acsptsci.1c00134. eCollection 2021 Oct 8.
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.
蛋白酶消化的乳铁蛋白片段通常表现出更好的治疗特性。然而，对这些片段的抗癌特性进行研究的报道有限。具有增强抗癌活性的片段是一种有吸引力的替代化疗药物的选择，因为化疗药物存在严重的副作用。在此，我们报告了重组工程乳铁蛋白（rtHLF4）的分离和特性，与全长乳铁蛋白（flHLF）相比，其抗癌活性提高了100倍。此外，rtHLF4能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上调了各种促凋亡标志物，并下调了参与血管生成和转移的信号蛋白。我们进一步确定，rtHLF4在高浓度下没有溶血活性。我们相信这种抗癌蛋白可以进一步开发用于癌症治疗。
