Protein-Nanocaged Selenium Induces t(8;21) Leukemia Cell Differentiation via Epigenetic Regulation.
Long FangRuofei ZhangLin ShiJiaying XieLong MaYili YangXiyun YanKelong FanPublished in: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (2023)
The success of arsenic in degrading PML-RARα oncoprotein illustrates the great anti-leukemia value of inorganics. Inspired by this, the therapeutic effect of inorganic selenium on t(8; 21) leukemia is studied, which has shown promising anti-cancer effects on solid tumors. A leukemia-targeting selenium nanomedicine is rationally built with bioengineered protein nanocage and is demonstrated to be an effective epigenetic drug for inducing the differentiation of t(8;21) leukemia. The selenium drug significantly induces the differentiation of t(8;21) leukemia cells into more mature myeloid cells. Mechanistic analysis shows that the selenium is metabolized into bioactive forms in cells, which drives the degradation of the AML1-ETO oncoprotein by inhibiting histone deacetylases activity, resulting in the regulation of AML1-ETO target genes. The regulation results in a significant increase in the expression levels of myeloid differentiation transcription factors PU.1 and C/EBPα, and a significant decrease in the expression level of C-KIT protein, a member of the type III receptor tyrosine kinase family. This study demonstrates that this protein-nanocaged selenium is a potential therapeutic drug against t(8;21) leukemia through epigenetic regulation.
Keyphrases
- acute myeloid leukemia
- bone marrow
- induced apoptosis
- tyrosine kinase
- binding protein
- cell cycle arrest
- allogeneic hematopoietic stem cell transplantation
- poor prognosis
- protein protein
- dna methylation
- signaling pathway
- transcription factor
- gene expression
- dendritic cells
- long non coding rna
- oxidative stress
- immune response
- emergency department
- adverse drug
- drug induced
- pi k akt