ArticleProceedings of the National Academy of Sciences of the United States of America2005
Induction of lysosomal membrane permeabilization by compounds that activate p53-independent apoptosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 217 citations in OpenAlex.
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- Trapzyme as multimodal Janus nanoplatform for apoptosis-based immunotherapy of periodontitis.Bioactive materials · 2025Article
- Side-stepping the guardian of the genome: current cancer therapeutics targeting mutant p53.Frontiers in pharmacology · 2025Review
- Discovery of Potent IsoquinolinequinoneJournal of medicinal chemistry · 2024Article
- Targeting Lysosomes: A Strategy Against Chemoresistance in Cancer.Mini reviews in medicinal chemistry · 2024Review
- Identification of PPT1 as a lysosomal core gene with prognostic value in hepatocellular carcinoma.Bioscience reports · 2023Article
- Metal-Organic Layer Delivers 5-Aminolevulinic Acid and Porphyrin for Dual-Organelle-Targeted Photodynamic Therapy.Angewandte Chemie (International ed. in English) · 2023Article
- Review
- The Achilles' heel of cancer: targeting tumors via lysosome-induced immunogenic cell death.Cell death & disease · 2022Review
- Galactosyl- and glucosylsphingosine induce lysosomal membrane permeabilization and cell death in cancer cells.PloS one · 2022Article
- Multidrug Resistance in Cancer: Understanding Molecular Mechanisms, Immunoprevention and Therapeutic Approaches.Frontiers in oncology · 2022Review
- Integrin αRegenerative biomaterials · 2021Article
- Small-Molecule Inhibitors Targeting Proteasome-Associated Deubiquitinases.International journal of molecular sciences · 2021Review
- Autophagy and organelle homeostasis in cancer.Developmental cell · 2021Review
- Guided Antitumoural Drugs: (Imidazol-2-ylidene)(L)gold(I) Complexes Seeking Cellular Targets Controlled by the Nature of Ligand L.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Autophagy Triggers Tamoxifen Resistance in Human Breast Cancer Cells by Preventing Drug-Induced Lysosomal Damage.Cancers · 2021Article
- Promising Anti-Mitochondrial Agents for Overcoming Acquired Drug Resistance in Multiple Myeloma.Cells · 2021Review
- Repurposing old drugs as new inhibitors of the ubiquitin-proteasome pathway for cancer treatment.Seminars in cancer biology · 2021Review
- Dienone Compounds: Targets and Pharmacological Responses.Journal of medicinal chemistry · 2020Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The p53 protein activates cellular death programs through multiple pathways. Because the high frequency of p53 mutations in human tumors is believed to contribute to resistance to commonly used chemotherapeutic agents, it is important to identify drugs that induce p53-independent cell death and to define the mechanisms of action of such drugs. Here we screened a drug library (the National Cancer Institute mechanistic set; 879 compounds with diverse mechanisms of actions) and identified 175 compounds that induced caspase cleavage of cytokeratin-18 in cultured HCT116 colon cancer cells at <5 microM. Interestingly, whereas most compounds elicited a stronger apoptotic response in cells with functional p53, significant apoptosis was observed also in p53-null cells. A subset of 15 compounds showing weak or no dependence on p53 for induction of apoptosis was examined in detail. Of these compounds, 11 were capable of activating caspase-3 in enucleated cells. Seven such compounds with nonnuclear targets were found to induce lysosomal membrane permeabilization (LMP). Translocation of the lysosomal proteases cathepsin B and cathepsin D into the cytosol was observed after treatment with these drugs, and apoptosis was inhibited by pepstatin A, an inhibitor of cathepsin D. Apoptosis depended on Bax, suggesting that LMP induced a mitochondrial apoptotic pathway. We conclude that a large number of potential anticancer drugs induce p53-independent apoptosis and that LMP is a mediator of many such responses.
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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.