|Table of Contents|

Effect and molecular mechanism of acetylshikonin-induced ferroptosis in acute myelogenous leukemia HL-60 cells

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 14
Page:
2581-2588
Research Field:
Publishing date:

Info

Title:
Effect and molecular mechanism of acetylshikonin-induced ferroptosis in acute myelogenous leukemia HL-60 cells
Author(s):
LI Zihui1; ZHOU Zhihui2; WANG Rong1; LI Yuanyuan2; LI Hong1; 2; 3
1.Shaanxi University of Chinese Medicine,Shaanxi Xianyang 712046,China;2.The Second Affiliated Hospital of Shaanxi University of Chinese Medicine,Shaanxi Xianyang 712000,China;3.Pharmaceutical Factory,Shaanxi University of Chinese Medicine,Shaanxi Xianyang 712000,China.
Keywords:
acetylshikonin; HL-60 cells; ferroptosis
PACS:
R733.71
DOI:
10.3969/j.issn.1672-4992.2023.14.004
Abstract:
Objective:To explore the effect and molecular mechanism of acetylshikonin-induced ferroptosis in acute myelogenous leukemia HL-60 cells.Methods:HL-60 cells were intervened with 1 μg/mL,2 μg/mL,4 μg/mL and 8 μg/mL of acetylshikonin for 24 h and 48 h,and the effect of acetylshikonin on the proliferation of HL-60 cells was detected by CCK-8 assay.Western blot detected the expression levels of ferroptosis-related proteins,such as,transcriptional regulator p53,cystine/glutamate antiporter (XCT),glutathione peroxidase 4 (GPX4),membrane protein transferrin receptor 1 (TFR1/CD71) and ferritin heavy chain 1 (FTH1).GSH/GSSG detection kit was used to detect the changes of intracellular GSH and GSSG contents in HL-60 cells after 24 h intervention with different concentrations of acetylshikonin.HL-60 cells were co-treated with 4 μg/mL acetylshikonin and 0.1 μmol/L Ferrostatin-1 (Fer-1) for 24 h,and the expression levels of ferroptosis-related proteins,such as,p53,XCT,GPX4,CD71 and FTH1 were detected by Western blot.Results:Compared with the control group and the DMSO group,different concentrations of acetylshikonin had strong inhibitory effects on the proliferation of HL-60 cells.Acetylshikonin significantly increased the expression levels of p53 and CD71,significantly decreased the expression levels of XCT,GPX4 and FTH1,among which,4 μg/mL acetylshikonin intervened HL-60 cells for 24 h,and the expression level of each protein changed most obviously.Acetylshikonin significantly reduced the content of GSH (P＜0.000 1) and significantly increased the ratio of GSSG/GSH (P＜0.000 1).Fer-1 reversed markedly elevated expression levels of p53 and CD71 and markedly reduced expression levels of XCT,GPX4 and FTH1.Conclusion:On the one hand,acetylshikonin may promote ferroptosis in HL-60 cells by up-regulating the expression of p53,inhibiting the expression of XCT,reducing the content of GSH,then inhibiting the expression of GPX4.On the other hand,acetylshikonin may affect iron homeostasis in HL-60 cells and promote ferroptosis by up-regulating the expression of CD71 (TFR1) and down-regulating the expression of FTH1.

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Memo

Memo:
陕西省自然科学基础研究计划（编号：2019JM-224）；陕西省卫生健康科研项目（编号：2018D087）；陕西省卫生科研项目（编号：2016D030）；陕西中医药大学学科创新团队项目（编号：2019-YS03）
Last Update: 1900-01-01