ArticleFrontiers in pharmacology2020
Lapatinib Activates the Kelch-Like ECH-Associated Protein 1-Nuclear Factor Erythroid 2-Related Factor 2 Pathway in HepG2 Cells.
Article in Frontiers in pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 14 citations in OpenAlex.
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- Effect and mechanism of fisetin against the development of metabolic dysfunction-associated fatty liver disease.Scientific reports · 2025Article
- Lapatinib ameliorates skin fibrosis by inhibiting TGF-β1/Smad and non-Smad signaling pathway.Scientific reports · 2025Article
- Promoting reactive oxygen species accumulation to overcome tyrosine kinase inhibitor resistance in cancer.Cancer cell international · 2024Review
- The involvement of hepatic cytochrome P450s in the cytotoxicity of lapatinib.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- Intratumoral drug-releasing microdevices allow in situ high-throughput pharmaco phenotyping in patients with gliomas.Science translational medicine · 2023Article
- Single-cell and genetic multi-omics analysis combined with experiments confirmed the signature and potential targets of cuproptosis in hepatocellular carcinoma.Frontiers in cell and developmental biology · 2023Article
- Human chorion-derived mesenchymal stem cells suppress JAK2/STAT3 signaling and induce apoptosis of cholangiocarcinoma cell lines.Scientific reports · 2022Article
- The Effects of Bioactive Compounds from Blueberry and Blackcurrant Powder on Oat Bran Pastes: Enhancing In Vitro Antioxidant Activity and Reducing Reactive Oxygen Species in Lipopolysaccharide-Stimulated Raw264.7 Macrophages.Antioxidants (Basel, Switzerland) · 2021Article
- Activation of Nrf2 by Electrophiles Is Largely Independent of the Selenium Status of HepG2 Cells.Antioxidants (Basel, Switzerland) · 2021Article
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4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The receptor tyrosine kinase inhibitor lapatinib, indicated to treat patients with HER2-positive breast cancer in combination with capecitabine, can cause severe hepatotoxicity. Lapatinib is further associated with mitochondrial toxicity and accumulation of reactive oxygen species. The effect of lapatinib on the Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, the major cellular defense pathway against oxidative stress, has so far not been studied in detail. In the present study, we show that lapatinib (2-20 µM) activates the Keap1-Nrf2 pathway in HepG2 cells, a hepatocellular carcinoma-derived cell line, in a concentration-dependent manner upon 24 h of treatment. Lapatinib stabilized the transcription factor Nrf2 at concentrations ≥5 µM and caused its nuclear translocation. Well-established Nrf2 regulated genes (
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