Novel Insights in the Regulatory Mechanisms of Ferroptosis in Hepatocellular Carcinoma

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2022 Jun 6

PMID 35663406

Authors

Shiwen Ma

Yao Mawulikplimi Adzavon

Xiaohu Wen

Pengxiang Zhao

Fei Xie

Mengyu Liu

Xuemei Ma

Affiliations

Soon will be listed here.

Abstract

Ferroptosis is a newly defined programmed cell death, which by its mechanism differs from other programmed cell death processes such as apoptosis, necrosis, and autophagy. It has a unique morphology and biological properties that antioxidants and iron-chelating agents can regulate. Ferroptosis has the characteristics of iron ion deposition and dependence on lipid peroxidation. It can affect the progression of many cancers, including liver cancer, by inducing an intracellular iron-dependent accumulation of reactive oxygen species, providing new possibilities for cancer treatment. At present, great progress has been made in exploring the molecular mechanism of ferroptosis. In this review, we summarize the characteristics, mechanisms, and regulatory factors of ferroptosis in detail, discuss the progress of ferroptosis research in liver cancer, and provide directions and new ideas for the treatment of hepatocellular carcinoma.

Citing Articles

Broadening horizons: research on ferroptosis in lung cancer and its potential therapeutic targets.

Gao G, Zhang X Front Immunol. 2025; 16:1542844.

PMID: 39917300 PMC: 11799241. DOI: 10.3389/fimmu.2025.1542844.

Ferroptosis resistance in cancer cells: nanoparticles for combination therapy as a solution.

Adzavon K, Zhao W, He X, Sheng W Front Pharmacol. 2024; 15:1416382.

PMID: 38962305 PMC: 11219589. DOI: 10.3389/fphar.2024.1416382.

The Importance and Essentiality of Natural and Synthetic Chelators in Medicine: Increased Prospects for the Effective Treatment of Iron Overload and Iron Deficiency.

Kontoghiorghes G Int J Mol Sci. 2024; 25(9).

PMID: 38731873 PMC: 11083551. DOI: 10.3390/ijms25094654.

Nuclear and cytoplasmic specific RNA binding proteome enrichment and its changes upon ferroptosis induction.

Sun H, Fu B, Qian X, Xu P, Qin W Nat Commun. 2024; 15(1):852.

PMID: 38286993 PMC: 10825125. DOI: 10.1038/s41467-024-44987-9.

Pien-Tze-Huang prevents hepatocellular carcinoma by inducing ferroptosis via inhibiting SLC7A11-GSH-GPX4 axis.

Yan X, Liu Y, Li C, Mao X, Xu T, Hu Z Cancer Cell Int. 2023; 23(1):109.

PMID: 37280673 PMC: 10246043. DOI: 10.1186/s12935-023-02946-2.

References

Verga Falzacappa M, Muckenthaler M . Hepcidin: iron-hormone and anti-microbial peptide. Gene. 2005; 364:37-44. DOI: 10.1016/j.gene.2005.07.020. View

Hattori K, Ishikawa H, Sakauchi C, Takayanagi S, Naguro I, Ichijo H . Cold stress-induced ferroptosis involves the ASK1-p38 pathway. EMBO Rep. 2017; 18(11):2067-2078. PMC: 5666609. DOI: 10.15252/embr.201744228. View

Kim E, Wong S, Martinez J . Programmed Necrosis and Disease:We interrupt your regular programming to bring you necroinflammation. Cell Death Differ. 2018; 26(1):25-40. PMC: 6294794. DOI: 10.1038/s41418-018-0179-3. View

Shan Y, Yang G, Huang H, Zhou Y, Hu X, Lu Q . Ubiquitin-Like Modifier Activating Enzyme 1 as a Novel Diagnostic and Prognostic Indicator That Correlates With Ferroptosis and the Malignant Phenotypes of Liver Cancer Cells. Front Oncol. 2020; 10:592413. PMC: 7744729. DOI: 10.3389/fonc.2020.592413. View

Liang C, Zhang X, Yang M, Dong X . Recent Progress in Ferroptosis Inducers for Cancer Therapy. Adv Mater. 2019; 31(51):e1904197. DOI: 10.1002/adma.201904197. View

Chang L, Chiang S, Chen S, Yu Y, Chou R, Chang W . Heme oxygenase-1 mediates BAY 11-7085 induced ferroptosis. Cancer Lett. 2017; 416:124-137. DOI: 10.1016/j.canlet.2017.12.025. View

Stockwell B, Jiang X . The Chemistry and Biology of Ferroptosis. Cell Chem Biol. 2020; 27(4):365-375. PMC: 7204503. DOI: 10.1016/j.chembiol.2020.03.013. View

Vashchenko G, MacGillivray R . Multi-copper oxidases and human iron metabolism. Nutrients. 2013; 5(7):2289-313. PMC: 3738974. DOI: 10.3390/nu5072289. View

Wang M, Yu F, Li P . Circular RNAs: Characteristics, Function and Clinical Significance in Hepatocellular Carcinoma. Cancers (Basel). 2018; 10(8). PMC: 6116001. DOI: 10.3390/cancers10080258. View

10.

Yan B, Ai Y, Sun Q, Ma Y, Cao Y, Wang J . Membrane Damage during Ferroptosis Is Caused by Oxidation of Phospholipids Catalyzed by the Oxidoreductases POR and CYB5R1. Mol Cell. 2020; 81(2):355-369.e10. DOI: 10.1016/j.molcel.2020.11.024. View

11.

Wang Y, Wei Z, Pan K, Li J, Chen Q . The function and mechanism of ferroptosis in cancer. Apoptosis. 2020; 25(11-12):786-798. DOI: 10.1007/s10495-020-01638-w. View

12.

Sun X, Ou Z, Chen R, Niu X, Chen D, Kang R . Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells. Hepatology. 2015; 63(1):173-84. PMC: 4688087. DOI: 10.1002/hep.28251. View

13.

Chen X, Kang R, Kroemer G, Tang D . Targeting ferroptosis in pancreatic cancer: a double-edged sword. Trends Cancer. 2021; 7(10):891-901. DOI: 10.1016/j.trecan.2021.04.005. View

14.

Braymer J, Freibert S, Rakwalska-Bange M, Lill R . Mechanistic concepts of iron-sulfur protein biogenesis in Biology. Biochim Biophys Acta Mol Cell Res. 2020; 1868(1):118863. DOI: 10.1016/j.bbamcr.2020.118863. View

15.

Yu Y, Xie Y, Cao L, Yang L, Yang M, Lotze M . The ferroptosis inducer erastin enhances sensitivity of acute myeloid leukemia cells to chemotherapeutic agents. Mol Cell Oncol. 2016; 2(4):e1054549. PMC: 4905356. DOI: 10.1080/23723556.2015.1054549. View

16.

Griffith O . Mechanism of action, metabolism, and toxicity of buthionine sulfoximine and its higher homologs, potent inhibitors of glutathione synthesis. J Biol Chem. 1982; 257(22):13704-12. View

17.

De Domenico I, Ward D, Kaplan J . Regulation of iron acquisition and storage: consequences for iron-linked disorders. Nat Rev Mol Cell Biol. 2007; 9(1):72-81. DOI: 10.1038/nrm2295. View

18.

Del Rey M, Mancias J . NCOA4-Mediated Ferritinophagy: A Potential Link to Neurodegeneration. Front Neurosci. 2019; 13:238. PMC: 6427834. DOI: 10.3389/fnins.2019.00238. View

19.

Shang Y, Luo M, Yao F, Wang S, Yuan Z, Yang Y . Ceruloplasmin suppresses ferroptosis by regulating iron homeostasis in hepatocellular carcinoma cells. Cell Signal. 2020; 72:109633. DOI: 10.1016/j.cellsig.2020.109633. View

20.

Mou Y, Wu J, Zhang Y, Abdihamid O, Duan C, Li B . Low expression of ferritinophagy-related NCOA4 gene in relation to unfavorable outcome and defective immune cells infiltration in clear cell renal carcinoma. BMC Cancer. 2021; 21(1):18. PMC: 7786469. DOI: 10.1186/s12885-020-07726-z. View