ArticleThe Prostate2017
Minnelide Inhibits Androgen Dependent, Castration Resistant Prostate Cancer Growth by Decreasing Expression of Androgen Receptor Full Length and Splice Variants.
Article in The Prostate, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Androgen receptor variant-driven prostate cancer II: advances in laboratory investigations.Prostate cancer and prostatic diseases · 2020Pooled it
- Minnelide ameliorates Col4a5+/- mice by upregulating Col4a5 and alleviating endoplasmic reticulum stress.Frontiers in pharmacology · 2026Article
- Natural Products Targeting the Androgen Receptor Signaling Pathway: Therapeutic Potential and Mechanisms.Current issues in molecular biology · 2025Review
- Antitumor mechanisms and future clinical applications of the natural product triptolide.Cancer cell international · 2024Review
- Article
- Minnelide Markedly Reduces Proteinuria in Mice with Adriamycin Nephropathy by Protecting Against Podocyte Injury.Applied biochemistry and biotechnology · 2023Article
- Triptolide inhibits epithelial ovarian tumor growth by blocking the hedgehog/Gli pathway.Aging · 2023Article
- Triptolide promotes ferroptosis by suppressing Nrf2 to overcome leukemia cell resistance to doxorubicin.Molecular medicine reports · 2023Article
- The Antigastric Cancer Effect of Triptolide is Associated With H19/NF-κB/FLIP Axis.Frontiers in pharmacology · 2022Article
- Identification of potential targets of triptolide in regulating the tumor microenvironment of stomach adenocarcinoma patients using bioinformatics.Bioengineered · 2021Article
- Triptolide: pharmacological spectrum, biosynthesis, chemical synthesis and derivatives.Theranostics · 2021Review
- Prostate cancer: Therapeutic prospect with herbal medicine.Current research in pharmacology and drug discovery · 2021Review
- Minnelide, a prodrug, inhibits cervical cancer growth by blocking HPV-induced changes in p53 and pRb.American journal of cancer research · 2021Article
- Development of Potential Antitumor Agents from the Scaffolds of Plant-Derived Terpenoid Lactones.Journal of medicinal chemistry · 2020Article
- [Arctiin antagonizes triptolide-induced renal toxicity in rats via anti-inflammatory pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2020Article
- The Roles of Plant-Derived Triptolide on Non-Small Cell Lung Cancer.Oncology research · 2019Review
- Pre-clinical evaluation of Minnelide as a therapy for acute myeloid leukemia.Journal of translational medicine · 2019Article
- Article
- A Mechanistic Overview of Triptolide and Celastrol, Natural Products fromFrontiers in pharmacology · 2018Review
- Allosteric alterations in the androgen receptor and activity in prostate cancer.Endocrine-related cancer · 2017Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundWith almost 30,000 deaths per year, prostate cancer is the second-leading cause of cancer-related death in men. Androgen Deprivation Therapy (ADT) has been the corner stone of prostate cancer treatment for decades. However, despite an initial response of prostate cancer to ADT, this eventually fails and the tumors recur, resulting in Castration Resistant Prostate Cancer (CRPC). Triptolide, a diterpene triepoxide, has been tested for its anti-tumor properties in a number of cancers for over a decade. Owing to its poor solubility in aqueous medium, its clinical application had been limited. To circumvent this problem, we have synthesized a water-soluble pro-drug of triptolide, Minnelide, that is currently being evaluated in a Phase 1 clinical trial against gastrointestinal tumors. In the current study, we assessed the therapeutic potential of Minnelide and its active compound triptolide against androgen dependent prostate cancer both in vitro as well as in vivo.
methodsCell viability was measured by a MTT based assay after treating prostate cancer cells with multiple doses of triptolide. Apoptotic cell death was measured using a caspase 3/7 activity. Androgen Receptor (AR) promoter-binding activity was evaluated by using luciferase reporter assay. For evaluating the effect in vivo, 22Rv1 cells were implanted subcutaneously in animals, following which, treatment was started with 0.21 mg/kg Minnelide.
resultsOur study showed that treatment with triptolide induced apoptotic cell death in CRPC cells. Triptolide treatment inhibited AR transcriptional activity and decreased the expression of AR and its splice variants both at the mRNA and the protein level. Our studies show that triptolide inhibits nuclear translocation of Sp1, resulting in its decreased transcriptional activity leading to downregulation of AR and its splice variants in prostate cancer cells. In vivo, Minnelide (0.21 mg/kg) regressed subcutaneous tumors derived from CRPC 22RV1 at our study endpoint. Our animal studies further confirmed that Minnelide was more efficacious than the standard of care therapies, Docetaxel and Enzalutamide.
conclusionOur study indicates that Minnelide is very effective as a therapeutic option against CRPC at a dose that is currently tolerated by patients in the ongoing clinical trials. Prostate 77: 584-596, 2017. © 2017 Wiley Periodicals, Inc.
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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.