ArticleCancer biology & therapy2011
Anticancer activity of Celastrol in combination with ErbB2-targeted therapeutics for treatment of ErbB2-overexpressing breast cancers.
Article in Cancer biology & therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Triterpenes in breast cancer: a systematic review of preclinical evidence in rodents.Frontiers in pharmacology · 2025Pooled it
- Computational techniques to study breast cancer scaffolds for antiangiogenesis: a review.Journal of molecular modeling · 2026Review
- Cytoplasmic Vacuolization: A Fascinating Morphological Alteration From Cellular Stress to Cell Death.Cancer science · 2025Review
- The effect of celastrol in combination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cell lines.Oncology research · 2024Article
- Withaferin A and Celastrol Overwhelm Proteostasis.International journal of molecular sciences · 2023Review
- Evolution of Natural Product Scaffolds as Potential Proteasome Inhibitors in Developing Cancer Therapeutics.Metabolites · 2023Review
- Celastrol suppresses the growth of vestibular schwannoma in mice by promoting the degradation of β-catenin.Acta pharmacologica Sinica · 2022Article
- SHP2 inhibition improves celastrol-induced growth suppression of colorectal cancer.Frontiers in pharmacology · 2022Article
- Celastrol inhibits ezrin-mediated migration of hepatocellular carcinoma cells.Scientific reports · 2020Article
- Chaperone mediated detection of small molecule target binding in cells.Nature communications · 2020Article
- Components from the Human c-myb Transcriptional Regulation System Reactivate Epigenetically Repressed Transgenes.International journal of molecular sciences · 2020Article
- Neuroprotective Effects of Celastrol on Transient Global Cerebral Ischemia Rats via Regulating HMGB1/NF-κB Signaling Pathway.Frontiers in neuroscience · 2020Article
- Celastrol Efficacy by Oral Administration in the Adjuvant-Induced Arthritis Model.Frontiers in medicine · 2020Article
- Celastrol: A Review of Useful Strategies Overcoming its Limitation in Anticancer Application.Frontiers in pharmacology · 2020Review
- Loss of the Nuclear Pool of Ubiquitin Ligase CHIP/STUB1 in Breast Cancer Unleashes the MZF1-Cathepsin Pro-oncogenic Program.Cancer research · 2018Article
- Inhibition of IKKβ by celastrol and its analogues - an in silico and in vitro approach.Pharmaceutical biology · 2017Article
- Protective effect of celastrol on myocardial ischemia-reperfusion injury.Anatolian journal of cardiology · 2017Article
- Targeting the ubiquitin-proteasome system for cancer treatment: discovering novel inhibitors from nature and drug repurposing.Cancer metastasis reviews · 2017Article
- Triptolide and celastrol loaded silk fibroin nanoparticles show synergistic effect against human pancreatic cancer cells.Nanoscale · 2017Article
- Compounds From Celastraceae Targeting Cancer Pathways and Their Potential Application in Head and Neck Squamous Cell Carcinoma: A Review.Current genomics · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The receptor tyrosine kinase ErbB2 is overexpressed in up to a third of breast cancers, allowing targeted therapy with ErbB2-directed humanized antibodies such as Trastuzumab. Concurrent targeting of ErbB2 stability with HSP90 inhibitors is synergistic with Trastuzumab, suggesting that pharmacological agents that can inhibit HSP90 as well as signaling pathways activated by ErbB2 could be useful against ErbB2-overexpressing breast cancers. The triterpene natural product Celastrol inhibits HSP90 and several pathways relevant to ErbB2-dependent oncogenesis including the NFκB pathway and the proteasome, and has shown promising activity in other cancer models. Here, we demonstrate that Celastrol exhibits in vitro antitumor activity against a panel of human breast cancer cell lines with selectivity towards those overexpressing ErbB2. Celastrol strongly synergized with ErbB2-targeted therapeutics Trastuzumab and Lapatinib, producing higher cytotoxicity with substantially lower doses of Celastrol. Celastrol significantly retarded the rate of growth of ErbB2-overexpressing human breast cancer cells in a mouse xenograft model with only minor systemic toxicity. Mechanistically, Celastrol not only induced the expected ubiquitinylation and degradation of ErbB2 and other HSP90 client proteins, but it also increased the levels of reactive oxygen species (ROS). Our studies show that the Michael Acceptor functionality in Celastrol is important for its ability to destabilize ErbB2 and exert its bioactivity against ErbB2-overexpressing breast cancer cells. These studies suggest the potential use of Michael acceptor-containing molecules as novel therapeutic modalities against ErbB2-driven breast cancer by targeting multiple biological attributes of the driver oncogene.
Indexed as
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.