Nickel carcinogenesis mechanism: cell cycle dysregulation
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Nickel carcinogenesis mechanism: cell cycle dysregulation Hongrui Guo 1,2 & Huidan Deng 1,2 & Huan Liu 1 & Zhijie Jian 1 & Hengmin Cui 1,2,3 & Jing Fang 1,2 & Zhicai Zuo 1,2 & Junliang Deng 1,2 & Yinglun Li 1,2 & Xun Wang 1,2 & Ling Zhao 1,2 Received: 17 July 2020 / Accepted: 18 November 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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 cyclindependent 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. Keywords Nickel . Cell cycle . G2/M . Carcinogenic mechanism
Introduction Nickel (Ni) is present in all soil types, meteorites, and volcanic eruptions (Das et al. 2018; Zambelli and Ciurli 2013). At low Responsible Editor: Mohamed M. Abdel-Daim Hongrui Guo, Huidan Deng, and Huan Liu contributed equally to this work. * Huidan Deng [email protected] * Hengmin Cui [email protected] 1
College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China
2
Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, Sichuan Agriculture University, Wenjiang, Chengdu 611130, China
3
Key Laboratory of Agricultural information engineering of Sichuan Province, Sichuan Agriculture University, Yaan, Sichuan 625014, China
concentration, it is regarded as an essential trace metal for animals, micro-organisms, plants, and humans; however, it is toxic at high concentration (Shahzad et al. 2018; Zambelli et al. 2016). The biological function of Ni has been known as enzyme constituent including urease, carbon monoxide dehydrogenase, hydrogenase, and methyl-S-coenzyme M reductase. Moreover, Ni plays a crucial role in DNA and RNA transmissions and is
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