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Nickel carcinogenesis mechanism: cell cycle dysregulation

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Abstract

Nickel (Ni) is a widely distributed metal in the environment and an important pollutant due to its widespread industrial applications. Ni has various toxicity in humans and experimental animals, including carcinogenicity. However, the carcinogenic effects of Ni remain troublesome. Cell cycle dysregulation may be an important carcinogenic mechanism and is also a potential molecular mechanism for Ni complexes anti-cancerous effects. Therefore, we conducted a literature review to summarize the effects of Ni on cell cycle. Up to now, there were three different reports on Ni-induced cell cycle arrest: (i) Ni can induce cell cycle arrest in G0/G1 phase, phosphorylation and degradation of IkappaB kinase-alpha (IKKα)–dependent cyclin D1 and phosphoinositide-3-kinase (PI3K)/serine-threonine kinase (Akt) pathway–mediated down-regulation of expressions of cyclin-dependent kinases 4 (CDK4) play important role in it; (ii) Ni can induce cell cycle arrest in S phase, but the molecular mechanism is not known; (iii) G2/M phase is the target of Ni toxicity, and Ni compounds cause G2/M cell cycle phase arrest by reducing cyclinB1/Cdc2 interaction through the activation of the ataxia telangiectasia mutated (ATM)-p53-p21 and ATM-checkpoint kinase inhibitor 1 (Chk1)/Chk2-cell division cycle 25 (Cdc25) pathways. Revealing the mechanisms of cell cycle dysregulation associated with Ni exposure may help in the prevention and treatment of Ni-related carcinogenicity and toxicology.

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Data availability

The present study data are available from the corresponding author on reasonable request.

Abbreviations

Ni:

nickel

IKKα:

IkappaB kinase-alpha

PI3K:

phosphoinositide-3-kinase

Akt:

serine-threonine kinase

ATM:

ataxia telangiectasia mutated

Chk:

checkpoint kinase inhibitor

Cdc25:

cell division cycle 25

CDK:

cyclin-dependent kinases

ROS:

reactive oxygen species

IARC:

International Agency for Research on Cancer; 8-OHdG: 8-hydroxy-2′-deoxyguanosine

CKIs:

cyclin-dependent kinase inhibitors

NRK:

normal rat kidney

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Funding

This review paper was supported by the program for Changjiang scholars and the university innovative research team (IRT 0848), the Shuangzhi project of Sichuan Agricultural University (03573050; 1921993267), and Sichuan Science and Technology Program (2020YJ0113)

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Author notes

  1. Hongrui Guo, Huidan Deng, and Huan Liu contributed equally to this work.

Authors and Affiliations

  1. College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu, 611130, China

    Hongrui Guo, Huidan Deng, Huan Liu, Zhijie Jian, Hengmin Cui, Jing Fang, Zhicai Zuo, Junliang Deng, Yinglun Li, Xun Wang & Ling Zhao

  2. Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu, 611130, China

    Hongrui Guo, Huidan Deng, Hengmin Cui, Jing Fang, Zhicai Zuo, Junliang Deng, Yinglun Li, Xun Wang & Ling Zhao

  3. Key Laboratory of Agricultural information engineering of Sichuan Province, Sichuan Agriculture University, Yaan, Sichuan, 625014, China

    Hengmin Cui

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  5. Hengmin Cui
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  6. Jing Fang
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  7. Zhicai Zuo
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  8. Junliang Deng
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  9. Yinglun Li
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  10. Xun Wang
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  11. Ling Zhao
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Contributions

Hongrui Guo and Hengmin Cui planned and designed the work. Hongrui Guo, Huidan Deng, Huan Liu, and Zhijie Jian were a major contributor in data collection and writing the manuscript. Hengmin Cui supervised the work. Hongrui Guo, Huidan Deng, Huan Liu, Zhijie Jian, Hengmin Cui, Jing Fang, Zhicai Zuo, Junliang Deng, Yinglun Li, Xun Wang, and Ling Zhao revised the manuscript. All the authors read and approved the manuscript.

Corresponding authors

Correspondence to Huidan Deng or Hengmin Cui.

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Guo, H., Deng, H., Liu, H. et al. Nickel carcinogenesis mechanism: cell cycle dysregulation. Environ Sci Pollut Res 28, 4893–4901 (2021). https://doi.org/10.1007/s11356-020-11764-2

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