ArticleScientific reports2017
Oridonin Triggers Chaperon-mediated Proteasomal Degradation of BCR-ABL in Leukemia.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Design, Synthesis and Biological Evaluation of Novel Oleanolic Acid Derivatives as Potential Anti-Leukemic Agents.Life (Basel, Switzerland) · 2026Article
- Natural Products Targeting BCR-ABL: A Plant-Based Approach to Chronic Myeloid Leukemia Treatment.Molecules (Basel, Switzerland) · 2025Review
- Article
- Research and Development Progression of Oridonin for Hematological Malignancies Therapy.Current medicinal chemistry · 2025Review
- A Potential Role for Oridonin in Cancer Control: Mechanisms of Autophagy and Apoptosis.Current cancer drug targets · 2025Review
- Modulating the tumor microenvironment: The role of traditional Chinese medicine in improving lung cancer treatment.Open life sciences · 2025Review
- HSF1 Activation Mechanisms, Disease Roles, and Small Molecule Therapeutics.International journal of biological sciences · 2025Review
- Enhancing cancer therapy: advanced nanovehicle delivery systems for oridonin.Frontiers in pharmacology · 2024Review
- A Cross-Talk about Radioresistance in Lung Cancer-How to Improve Radiosensitivity According to Chinese Medicine and Medicaments That Commonly Occur in Pharmacies.International journal of molecular sciences · 2023Review
- Oridonin inhibits SARS-CoV-2 replication by targeting viral proteinase and polymerase.Virologica Sinica · 2023Article
- Investigation of Flavonoid Scaffolds as DAX1 Inhibitors against Ewing Sarcoma through Pharmacoinformatic and Dynamic Simulation Studies.International journal of molecular sciences · 2023Article
- Targeting the PTP1B-Bcr-Abl1 interaction for the degradation of T315I mutant Bcr-Abl1 in chronic myeloid leukemia.Cancer science · 2023Article
- Artemisia vulgaris inhibits BCR/ABL and promotes apoptosis in chronic myeloid leukemia cells.Biomedical reports · 2022Article
- Chaperone-assisted E3 ligase CHIP: A double agent in cancer.Genes & diseases · 2022Review
- Ubiquitin ligases: guardians of mammalian development.Nature reviews. Molecular cell biology · 2022Review
- Computational Identification of BCR-ABL Oncogenic Signaling as a Candidate Target of Withaferin A and Withanone.Biomolecules · 2022Article
- Jiyuan oridonin A induces differentiation of acute myeloid leukemia cells including leukemic stem-like cells.Frontiers in pharmacology · 2022Article
- Biophysical and biochemical properties of PHGDH revealed by studies on PHGDH inhibitors.Cellular and molecular life sciences : CMLS · 2021Article
- Review
- Terpenoids' anti-cancer effects: focus on autophagy.Apoptosis : an international journal on programmed cell death · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inducing degradation of oncoproteins by small molecule compounds has the potential to avoid drug resistance and therefore deserves to be exploited for new therapies. Oridonin is a natural compound with promising antitumor efficacy that can trigger the degradation of oncoproteins; however, the direct cellular targets and underlying mechanisms remain unclear. Here we report that oridonin depletes BCR-ABL through chaperon-mediated proteasomal degradation in leukemia. Mechanistically, oridonin poses oxidative stress in cancer cells and directly binds to cysteines of HSF1, leading to the activation of this master regulator of the chaperone system. The resulting induction of HSP70 and ubiquitin proteins and the enhanced binding to CHIP E3 ligase hence target BCR-ABL for ubiquitin-proteasome degradation. Both wild-type and mutant forms of BCR-ABL can be efficiently degraded by oridonin, supporting its efficacy observed in cultured cells as well as mouse tumor xenograft assays with either imatinib-sensitive or -resistant cells. Collectively, our results identify a novel mechanism by which oridonin induces rapid degradation of BCR-ABL as well as a novel pharmaceutical activator of HSF1 that represents a promising treatment for leukemia.
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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.