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NK-18, a promising antimicrobial peptide: anti-multidrug resistant leukemia cells and LPS neutralizing properties
Biochimie ( IF 3.9 ) Pub Date : 2018-02-07 , DOI: 10.1016/j.biochi.2018.02.001
Jiexi Yan , Xiaolei Liang , Caijuan Bai , Lanxia Zhou , Juan Li , Kairong Wang , Yan Tang , Li Zhao

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.



中文翻译:

NK-18,一种有前途的抗菌肽:抗多药耐药的白血病细胞和LPS中和特性

随着多药耐药性的增加,需要具有多种作用机制的新型抗白血病药来应对这一挑战。NK-18是哺乳动物衍生蛋白NK-溶素的核心区域,可有效抑制多药耐药和敏感白血病细胞系的生存能力。同时,这种增殖抑制作用在敏感和多药耐药的白血病细胞系之间并不明显。NK-18显示出非致瘤细胞和致瘤细胞之间的选择性。它优先结合其外部小叶具有高磷脂酰丝氨酸含量的肿瘤细胞。NK-18通过在细胞膜上迅速形成孔而作用于多药耐药性白血病细胞系,对于K562 / ADM细胞而言,发展对NK-18的耐药性并不容易。此外,NK-18可以通过静电吸引来中和脂多糖并减少NO的产生。这些研究数据表明,与传统的化学疗法相比,NK-18在多药耐药性白血病治疗中具有巨大优势,并且可能成为进一步研究的潜在候选者。

更新日期:2018-02-07
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