A novel coumarin derivative DBH2 inhibits proliferation and induces apoptosis of chronic myeloid leukemia cells

Jiajia Xin; Huijie Zhang; Dandan Yin; Ning An; Yaozhen Chen; Jinmei Xu; Jing Zhang; Zhixin Liu; Yongsheng Liu; Wen Yin; Mingkai Li; Xingbin Hu

doi:10.1016/j.gendis.2022.08.021

您当前的位置：

首页 >

文章列表页 >

A novel coumarin derivative DBH2 inhibits proliferation and induces apoptosis of chronic myeloid leukemia cells

Full-length article | 更新时间：2023-05-16

- A novel coumarin derivative DBH2 inhibits proliferation and induces apoptosis of chronic myeloid leukemia cells
- A novel coumarin derivative DBH2 inhibits proliferation and induces apoptosis of chronic myeloid leukemia cells
- Genes & Diseases 2023年10卷第2期
- 作者机构：
  
  1. Department of Hematology, Tangdu Hospital, Air Force Medical University,Shaanxi,Xi’an,China,710038
  2. Department of Blood Transfusion, Xijing Hospital, Air Force Medical University,Shaanxi,Xi’an,China,710032
  3. Department of Pharmacology, School of Pharmacy, Air Force Medical University,Shaanxi,Xi’an,China,710032
  4. Key Laboratory of Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University,Chongqing,China,400016
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2022.08.021
  中图分类号：
- 纸质出版日期：2023，
  
  网络出版日期：2023-3-1，
扫描看全文
A novel coumarin derivative DBH2 inhibits proliferation and induces apoptosis of chronic myeloid leukemia cells[J]. Genes & Diseases, 2023,10(2).

Jiajia Xin, Huijie Zhang, Dandan Yin, et al. A novel coumarin derivative DBH2 inhibits proliferation and induces apoptosis of chronic myeloid leukemia cells[J]. Genes & Diseases, 2023,10(2).
A novel coumarin derivative DBH2 inhibits proliferation and induces apoptosis of chronic myeloid leukemia cells[J]. Genes & Diseases, 2023,10(2). DOI： 10.1016/j.gendis.2022.08.021.

Jiajia Xin, Huijie Zhang, Dandan Yin, et al. A novel coumarin derivative DBH2 inhibits proliferation and induces apoptosis of chronic myeloid leukemia cells[J]. Genes & Diseases, 2023,10(2). DOI： 10.1016/j.gendis.2022.08.021.

摘要

Abstract

With the development of tyrosine kinase inhibitor (TKI) resistance

finding the novel effective chemotherapeutic agent is of seminal importance for chronic myelogenous leukemia (CML) treatment. This study aims to find the effective anti-leukemic candidates and investigate the possible underlying mechanism. We synthesized the novel coumarin derivatives and evaluated their anti-leukemic activity. Cell viability assay revealed that compound DBH2 exhibited the potent inhibitory activity on the proliferation of CML K562 cells and TKI resistant K562 cells. Morphological observation and flow cytometry confirmed that DBH2 could selectively induce cell apoptosis and cell cycle arrest at G2/M phase of the K562 cells

which was further confirmed on the bone marrow cells from CML transgenic model mice and CD34

bone marrow leukemic cells from CML patients. Treatments of DBH2 in combination with imatinib could prolong the survival rate of SCL-tTA-BCR/ABL transgenic model mice significantly. Quantitative RT-PCR revealed that DBH2 inhibited the expression of STAT3 and STAT5 in K562 cells

and

caspase-3

knockout alleviated the DBH2 induced apoptosis. Furthermore

DBH2 could induce the expression of PARP1 and ROCK1 in K562 cells

which may play the important role in caspase-dependent apoptosis. Our results concluded that coumarin derivative DBH2 serves as a promising candidate for the CML treatment

especially in the combination with imatinib for the TKI resistant CML

and STAT/caspase-3 pathway was involved in the molecular mechanism of anti-leukemic activity of DBH2.

关键词

Keywords

ApoptosisCaspaseChronic myeloid leukemiaCoumarinSTAT

references

查看原文

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

The m6A regulator KIAA1429 stabilizes RAB27B mRNA and promotes the progression of chronic myeloid leukemia and resistance to targeted therapy

Autophagy-related lncRNAs in tumor progression and drug resistance: A double-edged sword

Zinc finger protein 831 promotes apoptosis and enhances chemosensitivity in breast cancer by acting as a novel transcriptional repressor targeting the STAT3/Bcl2 signaling pathway

Molecular and cellular pathophysiology of circulating cardiomyocyte-specific cell free DNA (cfDNA): Biomarkers of heart failure and potential therapeutic targets

PLSCR1 promotes apoptosis and clearance of retinal ganglion cells in glaucoma pathogenesis