ArticleJournal of biomedical science2022
Natural product myricetin is a pan-KDM4 inhibitor which with poly lactic-co-glycolic acid formulation effectively targets castration-resistant prostate cancer.
Article in Journal of biomedical science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Myricetin alleviates testosterone-induced benign prostatic hyperplasia by attenuating inflammation, oxidative stress, apoptosis and androgen signaling.Scientific reports · 2026Article
- The JMJD family histone demethylases: structure, mechanism of action, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- Targeting epigenetic regulators: In-silico discovery of natural inhibitors against histone demethylase KDM4C.PloS one · 2026Article
- Nanoparticle-based drug delivery systems in urologic oncology: From targeted therapy to precision theranostics.Materials today. Bio · 2025Review
- Investigating the Epigenetic Therapeutic Potential of Natural Compounds in Cancer.International journal of molecular sciences · 2025Review
- Review
- Microalgae-based Intestinal villi-targeting multistage biosystem for irritable bowel syndrome treatment.Nature communications · 2025Article
- KDM4C works in concert with GATA1 to regulate heme metabolism in head and neck squamous cell carcinoma.Cellular and molecular life sciences : CMLS · 2025Article
- Targeting N-Methyl-lysine Histone Demethylase KDM4 in Cancer: Natural Products Inhibitors as a Driving Force for Epigenetic Drug Discovery.ChemMedChem · 2025Review
- Dietary antioxidants and flavonoids are inversely associated with prostate cancer risk and mortality: evidence from NHANES and machine learning.Frontiers in nutrition · 2025Article
- The Pros and Cons of Estrogens in Prostate Cancer: An Update with a Focus on Phytoestrogens.Biomedicines · 2024Review
- The role of KDM4A-mediated histone methylation on temozolomide resistance in glioma cells through the HUWE1/ROCK2 axis.The Kaohsiung journal of medical sciences · 2024Article
- Myricetin: A Significant Emphasis on Its Anticancer Potential via the Modulation of Inflammation and Signal Transduction Pathways.International journal of molecular sciences · 2023Review
- Review
- The Role of ERα and ERβ in Castration-Resistant Prostate Cancer and Current Therapeutic Approaches.Biomedicines · 2023Review
- Recent studies on myricetin and its biological and pharmacological activities.EXCLI journal · 2023Article
- Synergistic effects of natural products in combination with anticancer agents in prostate cancer: A scoping review.Frontiers in pharmacology · 2022Article
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundCastration-resistant prostate cancer (CRPC) with sustained androgen receptor (AR) signaling remains a critical clinical challenge, despite androgen depletion therapy. The Jumonji C-containing histone lysine demethylase family 4 (KDM4) members, KDM4A‒KDM4C, serve as critical coactivators of AR to promote tumor growth in prostate cancer and are candidate therapeutic targets to overcome AR mutations/alterations-mediated resistance in CRPC.
methodsIn this study, using a structure-based approach, we identified a natural product, myricetin, able to block the demethylation of histone 3 lysine 9 trimethylation by KDM4 members and evaluated its effects on CRPC. A structure-based screening was employed to search for a natural product that inhibited KDM4B. Inhibition kinetics of myricetin was determined. The cytotoxic effect of myricetin on various prostate cancer cells was evaluated. The combined effect of myricetin with enzalutamide, a second-generation AR inhibitor toward C4-2B, a CRPC cell line, was assessed. To improve bioavailability, myricetin encapsulated by poly lactic-co-glycolic acid (PLGA), the US food and drug administration (FDA)-approved material as drug carriers, was synthesized and its antitumor activity alone or with enzalutamide was evaluated using in vivo C4-2B xenografts.
resultsMyricetin was identified as a potent α-ketoglutarate-type inhibitor that blocks the demethylation activity by KDM4s and significantly reduced the proliferation of both androgen-dependent (LNCaP) and androgen-independent CRPC (CWR22Rv1 and C4-2B). A synergistic cytotoxic effect toward C4-2B was detected for the combination of myricetin and enzalutamide. PLGA-myricetin, enzalutamide, and the combined treatment showed significantly greater antitumor activity than that of the control group in the C4-2B xenograft model. Tumor growth was significantly lower for the combination treatment than for enzalutamide or myricetin treatment alone.
conclusionsThese results suggest that myricetin is a pan-KDM4 inhibitor and exhibited potent cell cytotoxicity toward CRPC cells. Importantly, the combination of PLGA-encapsulated myricetin with enzalutamide is potentially effective for CRPC.
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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 Socratic graph.