Dataset Information

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.

SUBMITTER: Jin Y

PROVIDER: S-EPMC6245615 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Jin Yanxia Y Yang Qian Q Liang Li L Ding Lu L Liang Yuxing Y Zhang Dongdong D Wu Balu B Yang Tian T Liu Hailing H Huang Tingting T Shen Hui H Tu Honglei H Pan Yunbao Y Wei Yongchang Y Yang Yi Y Zhou Fuling F

Journal of experimental & clinical cancer research : CR 20181119 1

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>We found that intrac ...[more]

PMID: 30454068

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Project description:Traditional Chinese Medicine (TCM) preparations are often extracts of single or multiple herbs containing hundreds of compounds, and hence it has been difficult to study their mechanisms of action. Compound Kushen Injection (CKI) is a complex mixture of compounds extracted from two medicinal plants and has been used in Chinese hospitals to treat cancer for over twenty years. To demonstrate that a systematic analysis of molecular changes resulting from complex mixtures of bioactives from TCM can identify a core set of differentially expressed (DE) genes and a reproducible set of candidate pathways. We used in vitro cancer models to measure the effect of CKI on cell cycle phases and apoptosis, and correlated those phenotypes with CKI induced changes in gene expression. We treated two cancer cell lines with or without CKI and assessed the resulting phenotypes by employing cell viability and proliferation assays. Based on these results, we carried out high-throughput transcriptome data analysis to identify genes and candidate pathways perturbed by CKI. We integrated these differential gene expression results with previously reported results and carried out validation of selected differentially expressed genes. CKI induced cell-cycle arrest and apoptosis in the cancer cell lines tested. In these cells CKI also altered the expression of 363 core candidate genes associated with cell cycle, apoptosis, DNA replication/repair, and various cancer pathways. Of these, 7 are clinically relevant to cancer diagnosis or therapy, 14 are cell cycle regulators, and most of these 21 candidates are downregulated by CKI. Comparison of our core candidate genes to a database of plant medicinal compounds and their effects on gene expression identified one-to-one, one-to-many and many-to-many regulatory relationships between compounds in CKI and DE genes. By identifying genes and promising candidate pathways associated with CKI treatment based on our transcriptome-based analysis, we have shown that this approach is useful for the systematic analysis of molecular changes resulting from complex mixtures of bioactives.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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