ArticleOncotarget2018
Triptolide, a HSP90 middle domain inhibitor, induces apoptosis in triple manner.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 31 citations in OpenAlex.
- Anti-Cancer Research Progress of Triptolide: Mechanisms of Action, Structural Modifications, Nanodelivery Systems and Clinical Challenges.Drug design, development and therapy · 2026Review
- Protein modifications by advanced glycation end products (AGEs) in human clear cell renal cell carcinoma.Journal of translational medicine · 2025Article
- Establishment of interpretable cytotoxicity prediction models using machine learning analysis of transcriptome features.Acta pharmaceutica Sinica. B · 2025Article
- Paclitaxel mediates the PI3K/AKT/mTOR pathway to reduce proliferation of FLT3‑ITDExperimental and therapeutic medicine · 2024Article
- HSP90 Exacerbates Bone Destruction in Rheumatoid Arthritis by Activating TRAF6/NFATc1 Signaling.Inflammation · 2024Article
- Crystal structure of the middle and C-terminal domains of Hsp90α labeled with a coumarin derivative reveals a potential allosteric binding site as a drug target.Acta crystallographica. Section D, Structural biology · 2022Article
- Inhibitors of theCells · 2021Review
- Assay design and development strategies for finding Hsp90 inhibitors and their role in human diseases.Pharmacology & therapeutics · 2021Review
- Enhanced Photothermal Therapy through the In Situ Activation of a Temperature and Redox Dual-Sensitive Nanoreservoir of Triptolide.Small (Weinheim an der Bergstrasse, Germany) · 2020Article
- Allosteric Regulation of Hsp90α's Activity by Small Molecules Targeting the Middle Domain of the Chaperone.iScience · 2020Article
- Dynamically Shaping Chaperones. Allosteric Modulators of HSP90 Family as Regulatory Tools of Cell Metabolism in Neoplastic Progression.Frontiers in oncology · 2020Review
- Discovery of potential targets of Triptolide through inverse docking in ovarian cancer cells.PeerJ · 2020Article
- A Long Non-coding RNA Lnc712 Regulates Breast Cancer Cell Proliferation.International journal of biological sciences · 2020Article
- Identification of Isoform-Selective Ligands for the Middle Domain of Heat Shock Protein 90 (Hsp90).International journal of molecular sciences · 2019Article
- Cancer drug resistance: rationale for drug delivery systems and targeted inhibition of HSP90 family proteins.Cancer drug resistance (Alhambra, Calif.) · 2019Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triptolide (TL) is a potent anti-tumor, anti-inflammatory and immunosuppressive natural compound. Mechanistic studies revealed that TL inhibits tumor growth and triggers programmed cell death. Studies further suggested that TL inhibits heat shock response in cancer cells to induce apoptosis. HSP90β is the major component of heat shock response and is overexpressed in different types of cancers. Given almost all identified HSP90β inhibitors are either N or C-terminal inhibitors, small molecules attacking cysteine(s) in the middle domain might represent a new class of inhibitors. In the current study, we showed that TL inhibits HSP90β in triple manner. Characterization suggests that TL inhibits ATPase activity by preventing ATP binding thus blunts the chaperone activity. TL disrupts HSP90β-CDC37 (co-chaperone) complex through middle domain Cys366 of HSP90β and causes kinase client protein degradation. At the cellular level, the TL-mediated decrease in CDK4 protein levels in HeLa cells causes reduced phosphorylation of Rb resulting in cell cycle arrest at the G1 phase. Furthermore, our results demonstrated that TL triggers programmed cell death in an HSP90β-dependent manner as knockdown of HSP90β further sensitized TL-mediated cell cycle arrest and apoptotic effect. Surprisingly, our data showed that TL is the first drug to be reported to induce site-specific phosphorylation of HSP90β to drive apoptosome formation in the early phase of the treatment. In summary, our study established that TL is a novel middle domain HSP90β inhibitor with bi-phasic multi-mechanistic inhibition. The unique regulatory mechanism of TL on HSP90β makes it an effective inhibitor.
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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.