ArticleCarcinogenesis2015
A novel prostate cancer therapeutic strategy using icaritin-activated arylhydrocarbon-receptor to co-target androgen receptor and its splice variants.
Article in Carcinogenesis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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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
29 citing papers in PubMed, 66 citations in OpenAlex.
- Article
- Article
- Enhancer-targeting CRISPR screens at coronary artery disease loci suggest shared mechanisms of disease risk.medRxiv : the preprint server for health sciences · 2025Article
- Aryl hydrocarbon receptor as a drug target in advanced prostate cancer therapy - obstacles and perspectives.Transcription · 2025Review
- Icaritin-curcumol activates CD8Journal of experimental & clinical cancer research : CR · 2024Article
- Review
- Aryl Hydrocarbon Receptor as an Anticancer Target: An Overview of Ten Years Odyssey.Molecules (Basel, Switzerland) · 2023Review
- Multidisciplinary strategies to enhance therapeutic effects of flavonoids from Epimedii Folium: Integration of herbal medicine, enzyme engineering, and nanotechnology.Journal of pharmaceutical analysis · 2023Review
- The Impact of Indoles Activating the Aryl Hydrocarbon Receptor on Androgen Receptor Activity in the 22Rv1 Prostate Cancer Cell Line.International journal of molecular sciences · 2022Article
- Plant Occurring Flavonoids as Modulators of the Aryl Hydrocarbon Receptor.Molecules (Basel, Switzerland) · 2021Review
- Identification of low-frequency variants of UGT1A3 associated with bladder cancer risk by next-generation sequencing.Oncogene · 2021Article
- Icaritin inhibits PD-L1 expression by Targeting Protein IκB Kinase α.European journal of immunology · 2021Article
- Systems pharmacology dissection ofAging · 2021Article
- A comparative study on theDrug delivery · 2020Article
- Article
- Anticancer effect of icaritin on prostate cancer via regulating miR-381-3p and its target gene UBE2C.Cancer medicine · 2019Article
- Computer-Aided Discovery of Small Molecules Targeting the RNA Splicing Activity of hnRNP A1 in Castration-Resistant Prostate Cancer.Molecules (Basel, Switzerland) · 2019Article
- Reactive oxygen species induced by icaritin promote DNA strand breaks and apoptosis in human cervical cancer cells.Oncology reports · 2019Article
- Glucuronidation of icaritin by human liver microsomes, human intestine microsomes and expressed UDP-glucuronosyltransferase enzymes: identification of UGT1A3, 1A9 and 2B7 as the main contributing enzymes.Xenobiotica; the fate of foreign compounds in biological systems · 2018Article
- Genomic variants link to hepatitis C racial disparities.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
Persistent androgen receptor (AR) signaling is the key driving force behind progression and development of castration-resistant prostate cancer (CRPC). In many patients, AR COOH-terminal truncated splice variants (ARvs) play a critical role in contributing to the resistance against androgen depletion therapy. Unfortunately, clinically used antiandrogens like bicalutamide (BIC) and enzalutamide (MDV), which target the ligand binding domain, have failed to suppress these AR variants. Here, we report for the first time that a natural prenylflavonoid, icaritin (ICT), can co-target both persistent AR and ARvs. ICT was found to inhibit transcription of key AR-regulated genes, such as KLK3 [prostate-specific antigen (PSA)] and ARvs-regulated genes, such as UBE2C and induce apoptosis in AR-positive prostate cancer (PC) cells. Mechanistically, ICT promoted the degradation of both AR and ARvs by binding to arylhydrocarbon-receptor (AhR) to mediate ubiquitin-proteasomal degradation. Therefore, ICT impaired AR transactivation in PC cells. Knockdown of AhR gene restored AR stability and partially prevented ICT-induced growth suppression. In clinically relevant murine models orthotopically implanted with androgen-sensitive and CRPC cells, ICT was able to target AR and ARvs, to inhibit AR signaling and tumor growth with no apparent toxicity. Our results provide a mechanistic framework for the development of ICT, as a novel lead compound for AR-positive PC therapeutics, especially for those bearing AR splice variants.
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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.