ArticleOncotarget2017
Metformin alleviates nickel-induced autophagy and apoptosis via inhibition of hexokinase-2, activating lipocalin-2, in human bronchial epithelial cells.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 36 citations in OpenAlex.
- High expression of hexokinase 2 promotes lung cancer proliferation and metastasis.Archives of medical science : AMS · 2026Article
- Increased Lipocalin 2 detected by RNA sequencing regulates apoptosis and ferroptosis in COPD.BMC pulmonary medicine · 2024Article
- Heavy Metal Exposure: Molecular Pathways, Clinical Implications, and Protective Strategies.Antioxidants (Basel, Switzerland) · 2024Review
- Review
- Promising Strategy of mPTP Modulation in Cancer Therapy: An Emerging Progress and Future Insight.International journal of molecular sciences · 2023Review
- Induction of hemolysis and eryptosis by occupational pollutant nickel chloride is mediated through calcium influx and p38 MAP kinase signaling.International journal of occupational medicine and environmental health · 2022Article
- Nickel Sulfate Induces Autophagy in Human Thyroid Follicular Epithelial Cells.Biological trace element research · 2022Article
- p62 functions as a signal hub in metal carcinogenesis.Seminars in cancer biology · 2021Review
- Molecular mechanisms underlining the role of metformin as a therapeutic agent in lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2021Review
- Metformin Mitigates Nickel-Elicited Angiopoietin-Like Protein 4 Expression via HIF-1α for Lung Tumorigenesis.International journal of molecular sciences · 2020Article
- Metformin as a protective agent against natural or chemical toxicities: a comprehensive review on drug repositioning.Journal of endocrinological investigation · 2020Review
- Acute manganese treatment restores defective autophagic cargo loading in Huntington's disease cell lines.Human molecular genetics · 2019Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autophagy is an intracellular recycling and degradation process for regulating tumor progression, survival and drug resistance. Nickel compounds have been identified as human carcinogens. However, the role of nickel-induced autophagy in lung carcinogenesis has not yet been fully elucidated. In this study, we determined that hexokinase 2 (HK2), which phosphorylates glucose and regulates autophagy, is the key mediator in nickel-induced autophagy in lung bronchial epithelial cells. We attempted to investigate the effects of the antidiabetic drug metformin on HK2 expression and lung cancer chemoprevention. Our results showed that metformin decreases nickel-induced autophagy and activation of apoptosis through inhibition of HK2 gene, protein and activity. Furthermore, we demonstrated that lipocalin 2 (LCN2), which is released by neutrophils at sites of infection and inflammation is involved in HK2-driven autophagy pathway. Knockdown of endogenous HK2 and LCN2 by shRNA reduced nickel-elicited autophagy and apoptosis, illustrating that metabolic alteration and inflammatory action are important in nickel-elicited carcinogenesis. We also determined the association between nickel-induced autophagy and apoptosis. Inhibition of nickel-induced autophagy abolished apoptotic cell death in chloroquine-treated, shLC3 Beas-2B cells and Atg5
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