All-trans retinoic acid inhibits the malignant behaviors of hepatocarcinoma cells by regulating ferroptosis

Yanting Sun; Yun He; Jishuang Tong; Daijiang Liu; Haodong Zhang; Tongchuan He; Yang Bi

doi:10.1016/j.gendis.2022.04.011

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All-trans retinoic acid inhibits the malignant behaviors of hepatocarcinoma cells by regulating ferroptosis

更新时间：2022-11-09

- All-trans retinoic acid inhibits the malignant behaviors of hepatocarcinoma cells by regulating ferroptosis
- Genes & Diseases Vol. 9, Issue 6, (2022)
- 作者机构：
  
  1. Stem Cell Biology and Therapy Laboratory, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics,Chongqing,PR China,400014
  2. Department of Pediatric Surgery, Children's Hospital of Chongqing Medical University,Chongqing,PR China,400014
  3. Department of Gastroenterology, Chongqing Emergency Medical Centre,Chongqing,PR China,400014
  4. Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Centre,IL,Chicago,USA,60637
- 作者简介：
- 基金信息：
- DOI：10.1016/j.gendis.2022.04.011
  CLC：
- Published：2022，
  
  Published Online：1 November 2022，
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Yanting Sun, Yun He, Jishuang Tong, et al. All-trans retinoic acid inhibits the malignant behaviors of hepatocarcinoma cells by regulating ferroptosis. [J]. Genes & Diseases 9(6).(2022)
DOI：

Yanting Sun, Yun He, Jishuang Tong, et al. All-trans retinoic acid inhibits the malignant behaviors of hepatocarcinoma cells by regulating ferroptosis. [J]. Genes & Diseases 9(6).(2022) DOI： 10.1016/j.gendis.2022.04.011.

摘要

Abstract

ll-trans retinoic acid (ATRA) can reverse the malignant behaviors of hepatocellular carcinoma (HCC) cells

thereby exerting anti-HCC effect; however

the underlying mechanism is yet to be understood. This study aimed to demonstrate that ATRA is vital to ferroptosis in HCC. Ferroptosis-related genes exhibit different expression in patients with HCC compared to that in healthy individuals. A total of 20 amino acid products were detected in HepG2 cells

the expression level of 5 was decreased after ATRA treatment. ATRA improved the levels of lipid ROS

MDA

and NAPD

/NADPH

and reduced the mt-DNA copy number and changed the structure of mitochondria

in HepG2 and Hep3B cells. We found the expression of genes positively correlated with ferroptosis to increase and those negatively correlated to decrease with ATRA treatment. Inhibition of ferroptosis by Ferrostatin-1 reversed ATRA-inhibited proliferation of HCC cells

along with cell migration and invasion. GSH synthesis was blocked by ATRA

accompanied by decreased cystine content and increased glutamate content

and downregulation of the expression of GSH synthesis-related genes. Our findings suggested that ATRA inhibited the malignancy of HCC cells by improving ferroptosis

and that inhibition of GSH synthesis contributed to ATRA-induced ferroptosis.

关键词

Keywords

All-trans retinoic acidFerroptosisHepatocarcinomaInvasionMigration

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