Compound kushen injection suppresses human acute myeloid leukaemia by regulating the Prdxs/ROS/Trx1 signalling pathway

Compound kushen injection suppresses human acute myeloid leukaemia by regulating the Prdxs/ROS/Trx1 signalling pathway

Abstract

Background

The increase in the levels of reactive oxygen species (ROS) in acute myeloid leukemia (AML) patients has been previously described; thus, it is important to regulate ROS levels in AML.

Methods

Flow cytometry were used to assess the in vitro effect of compound kushen injection (CKI). Quantitative proteomics were used to analyse the mechanism. The AML patient-derived xenograft (PDX) model were used to evaluate the in vivo effect of CKI.

Results

We found that intracellular ROS levels in AML cells were decreased, the antioxidant capacity were increased when treated with CKI. CKI inhibited the proliferation of AML cells and enhanced the cytotoxicity of AML cells, which has few toxic effects on haematopoietic stem cells (HSCs) and T cells. At the single-cell level, individual AML cells died gradually by CKI treatment on optofluidic chips. CKI promoted apoptosis and arrested cell cycle at G1/G0 phase in U937 cells. Furthermore, higher peroxiredoxin-3 (Prdx3) expression levels were identified in CKI-treated U937 cells through quantitative proteomics detection. Mechanically, the expression of Prdx3 and peroxiredoxin-2 (Prdx2) was up-regulated in CKI-treated AML cells, while thioredoxin 1 (Trx1) was reduced. Laser confocal microscopy showed that the proteins Prdx2 could be Interacted with Trx1 by CKI treatment. In vivo, the survival was longer and the disease was partially alleviated by decreased CD45+ immunophenotyping in peripheral blood in the CKI-treated group in the AML PDX model.

Conclusions

Antioxidant CKI possess better clinical application against AML through the Prdxs/ROS/Trx1 signalling pathway.

Authors: Yanxia Jin, Qian Yang, Li Liang, Lu Ding, Yuxing Liang, Dongdong Zhang, Balu Wu, Tian Yang, Hailing Liu, Tingting Huang, Hui Shen, Honglei Tu, Yunbao Pan, Yongchang Wei, Yi Yang and Fuling Zhou

Influence Factor: 6.22

Citation: J Exp Clin Cancer Res 37, 277 (2018).

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