Engineering of Human Lactoferrin for Improved Anticancer Activity
Pan Yu, Niying Chua, Kaisheng Lim, Chun Loong Ho
Abstract
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.