Inhibitory Effect of Histone Deacetylase Inhibitor on the Proliferation of Leukemia Cells and Its Anti-Tumor Pharmacology

Shubo Wang

doi:10.4236/jbm.2021.91003

Abstract

The aim of this study was to explore the inhibitory effect of histone deacetylase inhibitor (HDACI) on the proliferation of leukemia cells. The two kinds of leukemia cells (human promyelocytic leukemia cell (HL-60) and human acute myelogenous leukemia cell (KG-1)) were selected for in vitro research. Besides, Chidamide, a kind of benzamide HDACI, was applied to induce and culture the HL-60 and KG-1 cells, and the anti-tumor cell proliferation activity of Chidamide on HL-60 and KG-1 was detected by the methyl thiazolyl tetrazolium (MTT) assay, which was 5.6 and 6.1 in turn. The cell scratch experiment verified that Chidamide had the metastasis inhibitory effect on HL-60 and KG-1 cells. Flow cytometry was employed to measure the percentage of apoptotic cells, and it was found that the percentage of apoptotic cells was 55.6% ± 1% and 48.6% ± 1% in sequence after HL-60 and KG-1 cells were treated with Chidamide for 36 hours. The number of auto-phagosomes was determined by transmission electron microscopy showing that the number of auto-phagosomes in HL-60 and KG-1 cells was 12 ± 1 and 10 ± 1, respectively after the induction process of Chidamide. The phosphorylated histone H2AX protein (γ-H2AX) recognition antibody immunofluorescence method was adopted to determine the deoxyribonucleic acid (DNA) damage, and the positive rates of HL-60 and KG-1 cells reached 28.41% and 26.35%, respectively after Chidamide treatment. Therefore, Chidamide, as a kind of HDACI, could effectively inhibit the proliferation of leukemia cells, so that the results of this experiment had a good guiding meaning for the clinical diagnosis and treatment of leukemia.

Highlights

At present, malignant tumors have become the number one killer of human health and one of the main causes of human death [1]
The anti-tumor proliferation activity of Chidamide on HL-60 and KG-1 cells was determined to be 5.6 and 6.1, respectively. It revealed that the membrane permeability of HL-60 and KG-1 molecules was positively affected under the effect of Chidamide, resulting in the high anti-proliferation activity of Chidamide against the two kinds of leukemia cells
It indicated that Chidamide had marked inhibitory effect on the metastasis of HL-60 and KG-1 leukemia cells

Summary

Introduction

Malignant tumors have become the number one killer of human health and one of the main causes of human death [1]. In traditional tumor treatment methods, the general method is to directly intervene in tumor cell mitosis and the synthesis and repair of DNA [2]. This treatment method is often accompanied by serious side effects, affecting the clinical treatment effect and leading to a great burden on the patient’s body. The basic mechanism of HDACI in the treatment of tumors is that the specific functions and groups in HDACI inhibit the structure of zinc finger (Zn2+) in HDAC [5]. In terms of cell performance, HDACI mainly manifests itself as inhibiting tumor cell growth, metastasis, and invasion, blocking the cell cycle, and inducing apoptosis [6], but the specific medicinal functions still need a lot of research data to prove

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Conclusion