ArticleScientific reports2016
Bafilomycin A1 induces caspase-independent cell death in hepatocellular carcinoma cells via targeting of autophagy and MAPK pathways.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 115 citations in OpenAlex.
- Beyond conventional therapies: the evolution of targeted agents and immunotherapies in triple-negative breast cancer.Acta pharmacologica Sinica · 2026Review
- Galectin-8 drives ERK-dependent mitochondrial fragmentation, perinuclear relocation and mitophagy, with metabolic adaptations for cell proliferation.European journal of cell biology · 2025Article
- Autophagy: The convergence point of aging and cancer.Biochemistry and biophysics reports · 2025Review
- Crosstalk Between Autophagy and Oxidative Stress in Hematological Malignancies: Mechanisms, Implications, and Therapeutic Potential.Antioxidants (Basel, Switzerland) · 2025Review
- Elimination of apoptotic cells by non-professional embryonic phagocytes can be stimulated or inhibited by external stimuli.Scientific reports · 2025Article
- Bafilomycin A1 induces colon cancer cell death through impairment of the endolysosome system dependent on iron.Scientific reports · 2025Article
- Gold nanoparticles synthesized from soil-derivedRSC advances · 2025Article
- Nuclear Magnetic Resonance Fingerprinting and Principal Component Analysis Strategies Lead to Anti-Tuberculosis Natural Product Discovery from Actinomycetes.Antibiotics (Basel, Switzerland) · 2025Article
- When Metal Complexes Evolve, and a Minor Species is the Most Active: the Case of Bis(Phenanthroline)Copper in the Catalysis of Glutathione Oxidation and Hydroxyl Radical Generation.Angewandte Chemie (International ed. in English) · 2025Article
- Inotodiol induces hepatocellular carcinoma apoptosis by activation of MAPK/ERK pathway.PloS one · 2025Article
- Autophagy and cancer therapy.Cancer letters · 2024Review
- Bafilomycin 1A Affects p62/SQSTM1 Autophagy Marker Protein Level and Autophagosome Puncta Formation Oppositely under Various Inflammatory Conditions in Cultured Rat Microglial Cells.International journal of molecular sciences · 2024Article
- Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Enhancing Therapeutic Efficacy in Cancer Treatment: Integrating Nanomedicine with Autophagy Inhibition Strategies.ACS omega · 2024Review
- The Evaluation of Drugs as Potential Modulators of the Trafficking and Maturation of ACE2, the SARS-CoV-2 Receptor.Biomolecules · 2024Article
- Cellular depletion of major cathepsin proteases reveals their concerted activities for lysosomal proteolysis.Cellular and molecular life sciences : CMLS · 2024Article
- Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail.Cancer research communications · 2024Article
- Bafilomycin A1 Molecular Effect on ATPase Activity of Subcellular Fraction of Human Colorectal Cancer and Rat Liver.International journal of molecular sciences · 2024Article
- Secretory mitophagy: an extracellular vesicle-mediated adaptive mechanism for cancer cell survival under oxidative stress.Frontiers in cell and developmental biology · 2024Article
- Unraveling the Janus-Faced Role of Autophagy in Hepatocellular Carcinoma: Implications for Therapeutic Interventions.International journal of molecular sciences · 2023Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is refractory to chemotherapies, necessitating novel effective agents. The lysosome inhibitor Bafilomycin A1 (BafA1) at high concentrations displays cytotoxicity in a variety of cancers. Here we show that BafA1 at nanomolar concentrations suppresses HCC cell growth in both 2 dimensional (2D) and 3D cultures. BafA1 induced cell cycle arrest in the G1 phase and triggered Cyclin D1 turnover in HCC cells in a dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) dependent manner. Notably, BafA1 induced caspase-independent cell death in HCC cells by impairing autophagy flux as demonstrated by elevated LC3 conversion and p62/SQSTM1 levels. Moreover, genetic ablation of LC3 significantly attenuated BafA1-induced cytotoxicity of HCC cells. We further demonstrate that pharmacological down-regulation or genetic depletion of p38 MAPK decreased BafA1-induced cell death via abolishment of BafA1-induced upregulation of Puma. Notably, knockdown of Puma impaired BafA1-induced HCC cell death, and overexpression of Puma enhanced BafA1-mediated HCC cell death, suggesting a role for Puma in BafA1-mediated cytotoxicity. Interestingly, pharmacological inhibition of JNK with SP600125 enhanced BafA1-mediated cytotoxicity both in vitro and in xenografts derived from HCC cells. Taken together, our data suggest that BafA1 may offer potential as an effective therapy for HCC.
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