ArticleCell death and differentiation2020
The antimalarial drug amodiaquine stabilizes p53 through ribosome biogenesis stress, independently of its autophagy-inhibitory activity.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 49 citations in OpenAlex.
- JP-1302 inhibits RNA polymerase I transcription and induces nucleolar stress in cancer cell lines.Cell death discovery · 2026Article
- Liposomal Amodiaquine for Localized Therapy of Non-Small Cell Lung Cancer (NSCLC).AAPS PharmSciTech · 2026Article
- Comparative Profiling and Chemogenomics Application of Chemical Tools for NR4A Nuclear Receptors.Journal of medicinal chemistry · 2025Article
- Ribosomal RNA transcription regulates splicing through ribosomal protein RPL22.Cell chemical biology · 2025Article
- The natural alkaloid nitidine chloride targets RNA polymerase I to inhibit ribosome biogenesis and repress cancer cell growth.Cell death discovery · 2025Article
- Amodiaquine ameliorates stress-induced premature cellular senescence via promoting SIRT1-mediated HR repair.Cell death discovery · 2024Article
- Ribosome biogenesis and ribosomal proteins in cancer stem cells: a new therapeutic prospect.Molecular biology reports · 2024Review
- Development of Nurr1 agonists from amodiaquine by scaffold hopping and fragment growing.Communications chemistry · 2024Article
- Article
- Chromatin damage generated by DNA intercalators leads to degradation of RNA Polymerase II.Nucleic acids research · 2024Article
- Nonsmall-cell lung cancer treatment: current status of drug repurposing and nanoparticle-based drug delivery systems.Turkish journal of biology = Turk biyoloji dergisi · 2024Article
- Actionable cancer vulnerability due to translational arrest, p53 aggregation and ribosome biogenesis stress evoked by the disulfiram metabolite CuET.Cell death and differentiation · 2023Article
- Small molecule-mediated disruption of ribosome biogenesis synergizes with FGFR inhibitors to suppress glioma cell growth.Neuro-oncology · 2023Article
- Therapeutic targeting of CNBP phase separation inhibits ribosome biogenesis and neuroblastoma progression via modulating SWI/SNF complex activity.Clinical and translational medicine · 2023Article
- Regulation of RNA Polymerase I Stability and Function.Cancers · 2022Review
- Exploring Amodiaquine's Repurposing Potential in Breast Cancer Treatment-Assessment of In-Vitro Efficacy & Mechanism of Action.International journal of molecular sciences · 2022Article
- 2-Guanidino-quinazoline promotes the readthrough of nonsense mutations underlying human genetic diseases.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- KLF16 enhances stress tolerance of colorectal carcinomas by modulating nucleolar homeostasis and translational reprogramming.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- p53 at the crossroad of DNA replication and ribosome biogenesis stress pathways.Cell death and differentiation · 2022Review
- Review
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pharmacological inhibition of ribosome biogenesis is a promising avenue for cancer therapy. Herein, we report a novel activity of the FDA-approved antimalarial drug amodiaquine which inhibits rRNA transcription, a rate-limiting step for ribosome biogenesis, in a dose-dependent manner. Amodiaquine triggers degradation of the catalytic subunit of RNA polymerase I (Pol I), with ensuing RPL5/RPL11-dependent stabilization of p53. Pol I shutdown occurs in the absence of DNA damage and without the subsequent ATM-dependent inhibition of rRNA transcription. RNAseq analysis revealed mechanistic similarities of amodiaquine with BMH-21, the first-in-class Pol I inhibitor, and with chloroquine, the antimalarial analog of amodiaquine, with well-established autophagy-inhibitory activity. Interestingly, autophagy inhibition caused by amodiaquine is not involved in the inhibition of rRNA transcription, suggesting two independent anticancer mechanisms. In vitro, amodiaquine is more efficient than chloroquine in restraining the proliferation of human cell lines derived from colorectal carcinomas, a cancer type with predicted susceptibility to ribosome biogenesis stress. Taken together, our data reveal an unsuspected activity of a drug approved and used in the clinics for over 30 years, and provide rationale for repurposing amodiaquine in cancer therapy.
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Registered trials
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.