ArticleOncology reports2020
Triptolide interrupts rRNA synthesis and induces the RPL23‑MDM2‑p53 pathway to repress lung cancer cells.
Article in Oncology reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Identification of potential genes and candidate drugs for intrahepatic cholestasis of pregnancy based on bioinformatics.Annals of medicine and surgery (2012) · 2026Article
- Anti-Cancer Research Progress of Triptolide: Mechanisms of Action, Structural Modifications, Nanodelivery Systems and Clinical Challenges.Drug design, development and therapy · 2026Review
- Pharmacological, computational, and mechanistic insights into triptolide's role in targeting drug-resistant cancers.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Traditional Chinese medicine in lung cancer treatment.Molecular cancer · 2025Review
- Histone Methyltransferase SETD1B Maintains Cancer Stem Cell Niche by Regulating the Crosstalk between CD24 and Surface Adhesion Molecules in Hepatocellular Carcinoma.International journal of biological sciences · 2025Article
- High-throughput transcriptome profiling indicates ribosomal RNAs to be associated with resistance to immunotherapy in non-small cell lung cancer (NSCLC).Journal for immunotherapy of cancer · 2024Article
- Antitumor mechanisms and future clinical applications of the natural product triptolide.Cancer cell international · 2024Review
- Article
- Potential association of HSPD1 with dysregulations in ribosome biogenesis and immune cell infiltration in lung adenocarcinoma: An integrated bioinformatic approach.Cancer biomarkers : section A of Disease markers · 2024Article
- The Effects of Deregulated Ribosomal Biogenesis in Cancer.Biomolecules · 2023Review
- Identification of three small nucleolar RNAs (snoRNAs) as potential prognostic markers in diffuse large B-cell lymphoma.Cancer medicine · 2023Article
- Review
- A Bibliometric Analysis of Triptolide and the Recent Advances in Treating Non-Small Cell Lung Cancer.Frontiers in pharmacology · 2022Review
- Application of herbal traditional Chinese medicine in the treatment of lupus nephritis.Frontiers in pharmacology · 2022Review
- UBTF facilitates melanoma progression via modulating MEK1/2-ERK1/2 signalling pathways by promoting GIT1 transcription.Cancer cell international · 2021Article
- Perspectives and controversies regarding the use of natural products for the treatment of lung cancer.Cancer medicine · 2021Review
- Triptolide: pharmacological spectrum, biosynthesis, chemical synthesis and derivatives.Theranostics · 2021Review
- Ribosomal Protein L23 Drives the Metastasis of Hepatocellular CarcinomaFrontiers in oncology · 2021Article
- Network pharmacology-based strategy for predicting therapy targets of Tripterygium wilfordii on acute myeloid leukemia.Medicine · 2020Article
- BCLAF1 induces cisplatin resistance in lung cancer cells.Oncology letters · 2020Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancer has one of the highest mortalities of any cancer worldwide. Triptolide (TP) is a promising tumor suppressor extracted from the Chinese herb Tripterygium wilfordii. Our previous proteomics analysis revealed that TP significantly interfered with the ribosome biogenesis pathway; however, the underlying molecular mechanism remains poorly understood. The aim of the present study was to determine the molecular mechanism of TP's anticancer effect by investigating the association between ribosomal stress and p53 activation. It was found that TP induces nucleolar disintegration together with RNA polymerase I (Pol I) and upstream binding factor (UBF) translocation. TP interrupted ribosomal (r)RNA synthesis through inhibition of RNA Pol I and UBF transcriptional activation. TP treatment increased the binding of ribosomal protein L23 (RPL23) to mouse double minute 2 protein (MDM2), resulting in p53 being released from MDM2 and stabilized. Activation of p53 induced apoptosis and cell cycle arrest by enhancing the activation of p53 upregulated modulator of apoptosis, caspase 9 and caspase 3, and suppressing BCL2. In vivo experiments showed that TP significantly reduced xenograft tumor size and increased mouse body weight. Immunohistochemical assays confirmed that TP significantly increased the p53 level and induced nucleolus disintegration, during which nucleolin distribution moved from the nucleolus to the nucleoplasm, and RPL23 clustered at the edge of the cell membrane. Therefore, it was proposed that TP induces ribosomal stress, which leads to nucleolus disintegration, and inhibition of rRNA transcription and synthesis, resulting in increased binding of RPL23 with MDM2. Consequently, p53 is activated, which induces apoptosis and cell cycle arrest.
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