ArticleThe Journal of biological chemistry2013
Nilotinib induces autophagy in hepatocellular carcinoma through AMPK activation.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 98 citations in OpenAlex.
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- Regulation of autophagy-mediated pathways by diet, physical activity, and sleep in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Targeting Lysosomes for Enhanced Anti-Cancer Therapeutics and Immune Response.International journal of biological sciences · 2026Review
- C9orf72-ALS mutation drives basal mitophagy impairments in iNeurons.Frontiers in cellular neuroscience · 2026Article
- The Rab3 family proteins in age-related neurodegeneration: unraveling molecular pathways and potential therapeutic targets.npj aging · 2025Review
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- High risk factors, molecular features and clinical management for radioactive iodine-refractory differentiated thyroid carcinoma.Frontiers in oncology · 2025Review
- Is Autophagy Targeting a Valid Adjuvant Strategy in Conjunction with Tyrosine Kinase Inhibitors?Cancers · 2024Review
- Nilotinib: Disrupting the MYC-MAX Heterocomplex.Bioinformatics and biology insights · 2024Article
- Tyrosine kinases: multifaceted receptors at the intersection of several neurodegenerative disease-associated processes.Frontiers in dementia · 2024Review
- Simultaneous activation and blockade of autophagy to fight hepatocellular carcinoma.Autophagy reports · 2024Article
- Integrated Analysis of N1-Methyladenosine Methylation Regulators-Related lncRNAs in Hepatocellular Carcinoma.Cancers · 2023Article
- Emerging Role of NLRP3 Inflammasome/Pyroptosis in Huntington's Disease.International journal of molecular sciences · 2022Review
- A novel AMPK activator shows therapeutic potential in hepatocellular carcinoma by suppressing HIF1α-mediated aerobic glycolysis.Molecular oncology · 2022Article
- Protein clearance strategies for disease intervention.Journal of neural transmission (Vienna, Austria : 1996) · 2022Review
- Construction of a Metabolism-Related Long Non-Coding RNAs-Based Risk Score Model of Hepatocellular Carcinoma for Prognosis and Personalized Treatment Prediction.Pathology oncology research : POR · 2022Article
- Signature construction and molecular subtype identification based on cuproptosis-related genes to predict the prognosis and immune activity of patients with hepatocellular carcinoma.Frontiers in immunology · 2022Article
- Mucin 1 as a Molecular Target of a Novel Diisoquinoline Derivative Combined with Anti-MUC1 Antibody in AGS Gastric Cancer Cells.Molecules (Basel, Switzerland) · 2021Article
- New Avenues for the Treatment of Huntington's Disease.International journal of molecular sciences · 2021Review
- A Structural Approach into Drug Discovery Based on Autophagy.Life (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is the most common liver cancer and the third-leading cause of cancer death worldwide. Nilotinib is an orally available receptor tyrosine kinase inhibitor approved for chronic myelogenous leukemia. This study investigated the effect of nilotinib on HCC. Nilotinib did not induce cellular apoptosis. Instead, staining with acridine orange and microtubule-associated protein 1 light chain 3 revealed that nilotinib induced autophagy in a dose- and time-dependent manner in HCC cell lines, including PLC5, Huh-7, and Hep3B. Moreover, nilotinib up-regulated the phosphryaltion of AMP-activated kinase (AMPK) and protein phosphatase PP2A inactivation were detected after nilotinib treatment. Up-regulating PP2A activity suppressed nilotinib-induced AMPK phosphorylation and autophagy, suggesting that PP2A mediates the effect of nilotinib on AMPK phosphorylation and autophagy. Our data indicate that nilotinib-induced AMPK activation is mediated by PP2A, and AMPK activation and subsequent autophagy might be a major mechanism of action of nilotinib. Growth of PLC5 tumor xenografts in BALB/c nude mice was inhibited by daily oral treatment with nilotinib. Western blot analysis showed both increased phospho-AMPK expression and decreased PP2A activity in vivo. Together, our results reveal that nilotinib induces autophagy, but not apoptosis in HCC, and that the autophagy-inducing activity is associated with PP2A-regulated AMPK phosphorylation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.