NK-18, a promising antimicrobial peptide: anti-multidrug resistant leukemia cells and LPS neutralizing properties

作者:Yan, Jiexi; Liang, Xiaolei; Bai, Caijuan; Zhou, Lanxia; Li, Juan; Wang, Kairong; Tang, Yan; Zhao, Li*
来源:Biochimie, 2018, 147: 143-152.
DOI:10.1016/j.biochi.2018.02.001

摘要

With the increase of multidrug resistance, novel anti-leukemia agents with diverse mechanisms of action are required to address this challenge. NK-18, the core region of mammalian derived protein NK-lysin, effectively inhibited the viability of both multidrug resistant and sensitive leukemia cell lines. Meanwhile, this proliferation inhibition effect was not distinct between sensitive and multidrug resistant leukemia cell line. NK-18 showed selectivity between non-tumorigenic and tumorigenic cells. It preferentially bound to tumor cells whose outer leaflet with high phosphatidylserine content. NK-18 acted on the multidrug resistant leukemia cell line by a rapid pore formation on the cell membrane, it is not easy for K562/ADM cells developing resistance against NK-18. Furthermore, NK-18 could neutralize lipopolysaccharides by electrostatic attraction and reduce NO production. These research data demonstrated NK-18 possesses great advantage in the multidrug resistant leukemia treatment compared with conventional chemotherapies and it could be a potential candidate for further research.