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A Stable Pep2-proapoptotic Peptide Inducing Apoptosis of Acute Myeloid Leukemia Cells by Down-Regulating EZH2.
Cellular and Molecular Bioengineering ( IF 2.3 ) Pub Date : 2019-12-04 , DOI: 10.1007/s12195-019-00605-z Yanli Sun 1 , Jiaqiu Li 2 , Yanhua Sun 3 , Ronglan Zhao 1 , Lujuan Wang 1 , Wei Song 1 , Zhanzhao Wang 4 , Jialing Wang 5 , Liuya Wei 6 , Yao Zhao 4 , Yang Song 1 , Zhenbo Hu 7
中文翻译:
一种通过下调 EZH2 诱导急性髓系白血病细胞凋亡的稳定 Pep2 促凋亡肽。
更新日期:2019-12-04
Cellular and Molecular Bioengineering ( IF 2.3 ) Pub Date : 2019-12-04 , DOI: 10.1007/s12195-019-00605-z Yanli Sun 1 , Jiaqiu Li 2 , Yanhua Sun 3 , Ronglan Zhao 1 , Lujuan Wang 1 , Wei Song 1 , Zhanzhao Wang 4 , Jialing Wang 5 , Liuya Wei 6 , Yao Zhao 4 , Yang Song 1 , Zhenbo Hu 7
Affiliation
Introduction
Proapoptotic peptide, (KLAKLAK)2, exhibits strong anti-tumor effect with the help of cell-penetrating peptides such as Pep2, targeting TLR2 with high expression in acute myeloid leukemia (AML). However, the applications are limited due to the peptide’s instability and high cost of synthesis. Recombinant PP7 bacteriophage-like particles (VLPs) can protect the peptides from degradation by proteases, based on their ability to display foreign peptides.Methods
Here, we evaluated the feasibility of PP7 VLPs carrying Pep2 and (KLAKLAK)2 (2PP7-Pep2-KLAK VLPs) expressed in E. coli. We further investigated the characteristics including size, toxicity, thermal stability, penetrating ability, anti-tumor activity, and potential anti-tumor mechanism of 2PP7-Pep2-KLAK VLPs.Results
2PP7-Pep2-KLAK VLPs was expressed in E. coli BL21(DE3) successfully with high yield and thermal stability. They penetrated the AML cells THP-1 rapidly after 30 min of incubation. Moreover, 2PP7-Pep2-KLAK VLPs were non-replicative, non-infectious, and non-toxic against normal cells, but inhibited the proliferation of THP-1 cells by inducing cell apoptosis after 24 h of exposure. This effect extends through 120 h of exposure, indicating their anti-proliferation effect was superior to that of synthetic peptides. In addition to the mitochondrial apoptotic pathway, the anti-tumor activity of 2PP7-Pep2-KLAK VLPs was also correlated with down-regulation of expression of enhancer of zeste homolog 2 (EZH2) and trimethylation of histone H3K27.Conclusions
We identified the feasibility to prepare the stable, active Pep2-KLAK peptide by using PP7 bacteriophage as the vehicle. We revealed this peptide was an inhibitor of EZH2. 2PP7-Pep2-KLAK VLPs may have significant clinical implications in the treatment of MLL-AF9 AML as an epigenetic modulator.中文翻译:
一种通过下调 EZH2 诱导急性髓系白血病细胞凋亡的稳定 Pep2 促凋亡肽。