ArticleLaboratory investigation; a journal of technical methods and pathology2021
Novel role of the dietary flavonoid fisetin in suppressing rRNA biogenesis.
Article in Laboratory investigation; a journal of technical methods and pathology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Overcoming Intrinsic and Acquired Temozolomide Resistance in Glioblastoma: Fisetin as a Potential Strategy to Enhance Sensitivity via ZEB1 Modulation.Turkish journal of pharmaceutical sciences · 2026Article
- Eight Triplex-Binding Molecules from Four Chemical Classes Broadly Recognize the MALAT1 Triple Helix.Molecules (Basel, Switzerland) · 2025Article
- Hypoxic stress incites HIF1α-driven ribosome biogenesis that can be exploited by targeting RNA Polymerase I.Nature communications · 2025Article
- Article
- Fisetin as a chemoprotective and chemotherapeutic agent: mechanistic insights and future directions in cancer therapy.Medical oncology (Northwood, London, England) · 2025Review
- Fisetin from Dietary Supplement to a Drug Candidate: An Assessment of Potential.Current pharmaceutical biotechnology · 2025Review
- Targeting EMT using low-dose Teniposide by downregulating ZEB2-driven activation of RNA polymerase I in breast cancer.Cell death & disease · 2024Article
- Biological effects and mechanisms of fisetin in cancer: a promising anti-cancer agent.European journal of medical research · 2023Review
- Fisetin in Cancer: Attributes, Developmental Aspects, and Nanotherapeutics.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Designing fisetin nanocrystals for enhancedInternational journal of pharmaceutics: X · 2022Article
- Ribosome Biogenesis: A Central Player in Cancer Metastasis and Therapeutic Resistance.Cancer research · 2022Review
- Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The nucleolus of a cell is a critical cellular compartment that is responsible for ribosome biogenesis and plays a central role in tumor progression. Fisetin, a nutraceutical, is a naturally occurring flavonol from the flavonoid group of polyphenols that has anti-cancer effects. Fisetin negatively impacts several signaling pathways that support tumor progression. However, effect of fisetin on the nucleolus and its functions were unknown. We observed that fisetin is able to physically enter the nucleolus. In the nucleolus, RNA polymerase I (RNA Pol I) mediates the biogenesis of ribosomal RNA. Thus, we investigated the impacts of fisetin on the nucleolus. We observed that breast tumor cells treated with fisetin show a 20-30% decreased nucleolar abundance per cell and a 30-60% downregulation of RNA Pol I transcription activity, as well as a 50-70% reduction in nascent rRNA synthesis, depending on the cell line. Our studies show that fisetin negatively influences MAPK/ERK pathway to impair RNA Pol I activity and rRNA biogenesis. Functionally, we demonstrate that fisetin acts synergistically (CI = 0.4) with RNA Pol I inhibitor, BMH-21 and shows a noteworthy negative impact (60% decrease) on lung colonization of breast cancer cells. Overall, our findings highlight the potential of ribosomal RNA (rRNA) biogenesis as a target for secondary prevention and possible treatment of metastatic disease.
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Registered trials
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