ArticleCell death discovery2020
Sempervirine inhibits RNA polymerase I transcription independently from p53 in tumor cells.
Article in Cell death discovery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- A selective NVL inhibitor suppresses tumor growth by targeting ribosome biogenesis.Nature chemical biology · 2026Article
- Dual RNA Polymerase I Inhibition with CX-5461 and BMH-21 Synergizes in Breast Cancer by Activating p53-Dependent Stress.bioRxiv : the preprint server for biology · 2025Article
- Bypassing the guardian: regulated cell death pathways in p53-mutant cancers.Cellular & molecular biology letters · 2025Review
- Sempervirine inhibits proliferation, invasion and metastasis of ovarian cancer cells and induces ultrastructural changes in vivo.Journal of ovarian research · 2025Article
- Antibacterial and antioxidant potentials, detection of host origin compounds, and metabolic profiling of endophytic Bacillus spp. isolated from Rauvolfia serpentina (L.) Benth. ex Kurz.Scientific reports · 2025Article
- Exploring the Mechanism of Sempervirine Inhibiting Glioblastoma Invasion Based on Network Pharmacology and Bioinformatics.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Recent progress in chemistry and bioactivity of monoterpenoid indole alkaloids from the genusJournal of enzyme inhibition and medicinal chemistry · 2023Review
- Article
- Regulation of RNA Polymerase I Stability and Function.Cancers · 2022Review
- Review
- Facing Counterfeit Medications in Sexual Medicine. A Systematic Scoping Review on Social Strategies and Technological Solutions.Sexual medicine · 2021Article
- Non-Coding RNAs and Splicing Activity in Testicular Germ Cell Tumors.Life (Basel, Switzerland) · 2021Review
- Sempervirine Inhibits Proliferation and Promotes Apoptosis by Regulating Wnt/β-Catenin Pathway in Human Hepatocellular Carcinoma.Frontiers in pharmacology · 2021Article
- Sempervirine Mediates Autophagy and ApoptosisFrontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
In the search of small molecules that can target MDM2/p53 pathway in testicular germ cell tumors (TGCTs), we identified sempervirine (2,3,4,13-tetrahydro-1H-benz[g]indolo[2,3-a]quinolizin-6-ium), an alkaloid of Gelsemium sempervirens, that has been previously proposed as an inhibitor of MDM2 that targets p53-wildtype (wt) tumor cells. We found that sempervirine not only affects cell growth of p53-wt cancer cells, but it is also active in p53-mutated and p53-null cells by triggering p53-dependent and independent pathways without affecting non-transformed cells. To understand which mechanism/s could be activated both in p53-wt and -null cells, we found that sempervirine induced nucleolar remodeling and nucleolar stress by reducing protein stability of RPA194, the catalytic subunit of RNA polymerase I, that led to rRNA synthesis inhibition and to MDM2 block. As shown for other cancer cell models, MDM2 inhibition by nucleolar stress downregulated E2F1 protein levels both in p53-wt and p53-null TGCT cells with the concomitant upregulation of unphosphorylated pRb. Finally, we show that sempervirine is able to enter the nucleus and accumulates within the nucleolus where it binds rRNA without causing DNA damage. Our results identify semperivirine as a novel rRNA synthesis inhibitor and indicate this drug as a non-genotoxic anticancer small molecule.
Identifiers
What OpenQuestion holds
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.