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

Abstract

BackgroundThe 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.MethodsFlow 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.ResultsWe 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.ConclusionsAntioxidant CKI possess better clinical application against AML through the Prdxs/ROS/Trx1 signalling pathway.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0948-3) contains supplementary material, which is available to authorized users.

Selenoprotein T protects against cisplatin‐induced acute kidney injury through suppression of oxidative stress and apoptosis

“…Numerous studies have shown that Trx1 plays an important role in ROS scavenging in various diseases through its protection against redox stress. [34][35][36][37][38] Moreover, the expression of Trx1 has been correlated with the activity of various Nox components, including Nox4, Nox2, p22 phox , and Rac. 39,40 Therefore, we presume that SelT may be a novel essential effector of the intracellular antioxidant system, which functions as Trx1, thus regulating Nox activity and ROS production.…”

Mechanisms of Compound Kushen Injection for the Treatment of Lung Cancer Based on Network Pharmacology

“…Matrine and oxymatrine are the primary active compounds in CKI and have antitumor effects in different cancer cells, including breast cancer cell lines (MCF-7), gastric cancer cells (SGC-7901 and MKN45), and human liver cancer cells (SMMC-7721) [13, 14]. Many clinical studies have confirmed that CKI can be used to treat malignant tumors by inducing apoptosis in tumor cells, as well as by inhibiting cancer cell proliferation and tumor growth, migration and invasion [13, 15, 16]. Moreover, a recent study has systematically investigated the mechanism of CKI in treating hepatocellular carcinoma based on a network pharmacology method [17].…”

Fractional Deletion Of Compound Kushen Injection, A Natural Compound Mixture, Indicates Cytokine Signaling Pathways Are Critical For Its Perturbation Of The Cell Cycle

“…Previous studies have demonstrated that CKI can alter the cell cycle, induce apoptosis and reduce proliferation in various cancer cell lines (Xu et al, 2011;Qu et al, 2016;Gao et al, 2018). CKI also killed leukaemia cells via the Prdxs/ROS/Trx1 signalling pathway in an acute myeloid leukaemia patient-derived xenograft model and caused cell cycle arrest in U937 leukaemia derived cells (Jin et al, 2018). Cell cycle arrest by CKI at checkpoints is correlated with the induction of double strand breaks by CKI treatment (Cui et al, 2018).…”