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Journal of Cancer Research and Clinical Oncology

, Volume 144, Issue 12, pp 2329–2337 | Cite as

Role of ferroptosis in hepatocellular carcinoma

  • Jianhua Nie
  • Binlin Lin
  • Meng Zhou
  • Li Wu
  • Tongsen ZhengEmail author
Review – Cancer Research

Abstract

Purpose

Hepatocellular carcinoma (HCC) is a complicated disease with low survival rate due to frequent recurrence and the lack of efficient therapies. For advanced HCC, sorafenib, as the only approved first-line drug for HCC, improves the survival to some extent, but depressingly with severe adverse effects and emerging resistance conditions, which cause a poor prognosis. Ferroptosis is a new recognized way of non-apoptosis-regulated cell death, characterized by the iron-dependent accumulation of lipid hydroperoxides, showing a tremendous promising in the therapy of cancer, especially in HCC. To provide ideas for the diagnosis and treatment of HCC, we summarized the role of ferroptosis in HCC.

Methods

The relevant literature from PubMed is reviewed in this article.

Results

Interestingly enough, investigators have found sorafenib can induce ferroptosis in HCC. Moreover, recent researches reported increasing pathways and mechanisms related to ferroptosis in HCC such as TP53 and Rb, and strategies to improve sorafenib resistance by targeting ferroptosis. In addition, other drugs were reported to induce ferroptosis in HCC such as erastin and showed good efficacy in vivo and in vitro.

Conclusion

In this review, we summarize pathways and mechanisms of ferroptosis in HCC and other digestive system neoplasms such as gastric cancer, pancreatic cancer and colorectal cancer and point out the trends of ferroptosis in HCC.

Keywords

Hepatocellular carcinoma Ferroptosis Sorafenib Lipid metabolism Iron Therapy 

Abbreviations

HCC

Hepatocellular carcinoma

RCD

Regulated cell death

NRF2

Nuclear factor erythroid 2-related factor 2

RPL8

Ribosomal protein L8

IREB2

Iron-responsive element-binding protein 2

ATP5G3

ATP synthase F0 complex subunit C3

CS

Citrate synthase

TTC35

Tetratricopeptide repeat domain 35

ACSF2

Acyl-CoA synthetase family member 2

GSH

Glutathione

ROS

Reactive oxygen species

GPX4

Glutathione peroxidase 4

DLBCL

Diffuse large B-cell lymphoma

RCC

Renal cell carcinoma

PC

Pancreatic cancer

SSZ

Sulfasalazine

DFX

Deferoxamine

Rb

Retinoblastoma

Keap1

Kelch-like ECH-associated protein 1

Maf

V-maf avian musculoaponeurotic fibrosarcoma oncogene homolog

NQO1

Quinone oxidoreductase 1

HO1

Heme oxygenase-1

FTH1

Ferritin heavy chain 1

MT

Metallothionein

HIF1α

Hypoxia-inducible factor 1-alpha

S1R

Sigma 1 receptor

CISD1

CDGSH iron sulfur domain 1

S47

Ser 47

ACSL4

Acyl-CoA synthetase long-chain family member 4

5-HETE

5-Hydroxyeicosatetraenoic acid

LDL–DHA

Low-density lipoprotein docosahexaenoic acid

GC

Gastric cancer

CRC

Colorectal cancer

CDO1

Cysteine dioxygenase 1

PDAC

Pancreatic ductal adenocarcinoma

CN-A

Cotylenin A

PEITC

Phenethyl isothiocyanate

PL

Piperlongumine

HSPA5

Heatshock 70-kDa protein 5

LOX

Lipoxygenases

ALOX

Arachidonate lipoxygenase

NCOA4

Nuclear receptor coactivator 4

CHOP

C/EBP-homologous protein

TRAIL

Tumor necrosis factor-related apoptosis-inducing ligand

DPP4

Dipeptidyl-peptidase-4

Notes

Acknowledgements

We are grateful to the staff at the GI oncology of cancer hospital of HMU. And we thank Kainan Kang for his critical reading of the manuscript.

Funding

This study was funded by the National Natural Scientific Foundation of China (No. 81302060, No.81472322 and No. 81672930), the national youth talent support program for TS Zheng, the Natural Science Foundation of Heilongjiang Province (LC201437/H1617), China Postdoctoral Science Foundation (No. 2015T80369 and No. 2014M560271), and Heilongjiang Postdoctoral Science Foundation (No. LBH-Z14142 and No. LBH-TZ1615), the Fok Ying Tung Education Foundation (No. 151037), the Academician Yu Weihan Outstanding youth foundation of Harbin Medical University for TS Zheng. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Compliance with ethical standards

Conflict of interest

Authors declare no conflict of interests.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Gastrointestinal Medical OncologyCancer Hospital of Harbin Medical UniversityHarbinPeople’s Republic of China
  2. 2.Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education)Harbin Medical UniversityHarbinPeople’s Republic of China

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