Nickel carcinogenesis mechanism: cell cycle dysregulation

Area of Science:

• Environmental Toxicology
• Molecular Carcinogenesis

Background:

• Nickel (Ni) is an environmental pollutant with known toxicity, including carcinogenicity in humans and animals.
• Cell cycle dysregulation is a key mechanism in cancer development and may also underlie nickel's anti-cancer effects.

Purpose of the Study:

• To review and summarize the known effects of nickel on the cell cycle.
• To elucidate the molecular mechanisms of nickel-induced cell cycle arrest.

Main Methods:

• Literature review of studies investigating nickel's impact on cell cycle progression.
• Analysis of reported molecular pathways involved in nickel-induced cell cycle arrest.

Main Results:

• Nickel induces G0/G1 phase arrest via IkappaB kinase-alpha (IKKα) and phosphoinositide-3-kinase (PI3K)/Akt pathways, affecting cyclin D1 and CDK4.
• Nickel can cause S phase arrest, though the underlying molecular mechanisms require further investigation.
• Nickel induces G2/M phase arrest by disrupting cyclinB1/Cdc2 interaction through ATM-p53-p21 and ATM-Chk1/Chk2-Cdc25 pathways.

Conclusions:

• Nickel exposure leads to cell cycle arrest at different phases (G0/G1, S, G2/M) through distinct molecular mechanisms.
• Understanding these nickel-induced cell cycle dysregulations is vital for developing strategies to prevent and treat nickel-related carcinogenicity and toxicity.