Apoptosis Induction in K562 Human Myelogenous Leukaemia Cells is Connected to the Modulation of Wnt/β-catenin Signalling by BHX, a Novel Pyrazoline Derivative

Overview

Journal Cell Prolif

Date 2018 Jan 18

PMID 29341317

Citations 4

Authors

Hanmei Bao

Qing Zhang

Yibo Du

Cai Zhang

Hui Xu

Zhongling Zhu

Zhao Yan

Affiliations

Soon will be listed here.

Abstract

Objectives: The goal of this study was to explore the effects of BHX on human chronic myeloid leukaemia (CML) cells and to elucidate the underlying molecular mechanism.

Materials And Methods: CML cell line K562 cells were treated with BHX. The effects of BHX on cell proliferation, apoptosis and cell cycle were detected. Subsequently, the caspase, ATP activity, Ca , ROS and mitochondrial membrane potential (MMP) levels treated with various concentrations of BHX were analysed. The variation of relevant proteins and genes was detected. Further, toxicity of BHX on peripheral blood cells, bone marrow-nucleated cells (BMNC) and organ index were investigated on mice.

Results: Results showed that BHX suppressed K562 cell proliferation in a dose-dependent manner and induced apoptosis and G0/G1 phase arrest. BHX induced mitochondria-mediated apoptosis, which was associated with downregulation of MMP, activation of caspase-3 and caspase-9, generation of intracellular ROS and elevation of Ca in K562 cells. In treated cells, ATP levels were decreased, expression of total β-catenin, phosphorylated β-catenin and β-catenin in the nucleus was decreased, and expression of cell cycle-related proteins was decreased. Further analysis revealed that BHX lowered the transcriptional level of β-catenin. Lastly, BHX treatment significantly reduced the number of white blood cells, but had no effect on BMNC and organ index.

Conclusions: These findings provide further insight into the potential use of BHX as an anti-cancer agent against human leukaemia.

Citing Articles

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Cui X, Wang Z, Li J, Zhu J, Ren Z, Zhang D Cell Prolif. 2020; 53(3):e12768.

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Moreno L, Quiroga J, Abonia R, Ramirez-Prada J, Insuasty B Molecules. 2018; 23(8).

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Apoptosis induction in K562 human myelogenous leukaemia cells is connected to the modulation of Wnt/β-catenin signalling by BHX, a novel pyrazoline derivative.

Bao H, Zhang Q, Du Y, Zhang C, Xu H, Zhu Z Cell Prolif. 2018; 51(3):e12433.

PMID: 29341317 PMC: 6528944. DOI: 10.1111/cpr.12433.

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