ArticleAnnals of surgical oncology2014
Hesperetin activates the Notch1 signaling cascade, causes apoptosis, and induces cellular differentiation in anaplastic thyroid cancer.
Article in Annals of surgical oncology, 2014. 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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Who cites it
29 citing papers in PubMed, 72 citations in OpenAlex.
- Notch signaling-targeted biomimetic hydrogel constructs an anti-inflammatory "flood-control" system to alleviate pyroptosis for intervertebral disc degeneration treatment.Materials today. Bio · 2026Article
- Updated Review on Natural Polyphenols: Molecular Mechanisms, Biological Effects, and Clinical Applications for Cancer Management.Biomolecules · 2025Review
- Notch signaling pathway modulation by food functional ingredients: mechanisms, cancer and immunoregulation.Frontiers in cell and developmental biology · 2025Review
- Promising Approaches in Plant-Based Therapies for Thyroid Cancer: An Overview of In Vitro, In Vivo, and Clinical Trial Studies.International journal of molecular sciences · 2024Review
- Exploring cell competition for the prevention and therapy of esophageal squamous cell carcinoma.Biochemical pharmacology · 2023Review
- Notch1 promotes resistance to cisplatin by up-regulating Ecto-5'-nucleotidase (CD73) in triple-negative breast cancer cells.Cell death discovery · 2023Article
- Hesperetin and Capecitabine Abate 1,2 Dimethylhydrazine-Induced Colon Carcinogenesis in Wistar Rats via Suppressing Oxidative Stress and Enhancing Antioxidant, Anti-Inflammatory and Apoptotic Actions.Life (Basel, Switzerland) · 2023Article
- Notch signaling pathway: architecture, disease, and therapeutics.Signal transduction and targeted therapy · 2022Review
- Modulation of Notch Signaling Pathway by Bioactive Dietary Agents.International journal of molecular sciences · 2022Review
- Chemotherapeutic potential of hesperetin for cancer treatment, with mechanistic insights: A comprehensive review.Heliyon · 2022Review
- Review
- Bioinformatics andAdvanced pharmaceutical bulletin · 2021Article
- NOTCH and Esophageal Squamous Cell Carcinoma.Advances in experimental medicine and biology · 2021Review
- Notch Signaling in Thyroid Cancer.Advances in experimental medicine and biology · 2021Review
- Combined tazemetostat and MAPKi enhances differentiation of papillary thyroid cancer cells harbouring BRAFJournal of cellular and molecular medicine · 2020Article
- Synergistic repression of thyroid hyperplasia by cyclin C and Pten.Journal of cell science · 2019Article
- Expression of NOTCH1 in thyroid cancer is mostly restricted to papillary carcinoma.Endocrine connections · 2019Article
- Therapeutic advances in anaplastic thyroid cancer: a current perspective.Molecular cancer · 2018Review
- Periostin silencing suppresses the aggressive phenotype of thyroid carcinoma cells by suppressing the Akt/thyroid stimulating hormone receptor axis.Cytotechnology · 2018Article
- PARP Inhibition by Flavonoids Induced Selective Cell Killing to BRCA2-Deficient Cells.Pharmaceuticals (Basel, Switzerland) · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAnaplastic thyroid cancer (ATC) is characterized by very aggressive growth with undifferentiated features. Recently, it has been reported that the Notch1 signaling pathway, which affects thyrocyte proliferation and differentiation, is inactivated in ATC. However, it remains largely unknown whether using Notch1 activating compounds can be an effective therapeutic strategy in ATC. Therefore, in this study, we aimed to evaluate the drug effects of a potential Notch activator hesperetin on ATC cell.
methodsA unique ATC cell line HTh7 was used to evaluate the drug effects of hesperetin. The Notch1 activating function and cell proliferation were evaluated. The mechanism of growth regulation was investigated by the detection of apoptotic markers. The expression levels of thyrocyte-specific genes were quantified for ATC redifferentiation.
resultsUpregulated expression of Notch1 and its downstream effectors hairy and enhancer of split 1 (Hes1) and Hes1 related with YRPW motif was observed in hesperetin-treated ATC cells. The enhanced luciferase signal also confirmed the functional activity of hesperetin-induced Notch1 signaling. Hesperetin led to a time- and dose-dependent decrease in ATC cell proliferation. The cell-growth inhibition was mainly caused by apoptosis as evidenced by increased levels of cleaved poly ADP ribose polymerase and cleaved caspase-3 as well as decreased survivin. Additionally, hesperetin induced the expression levels of thyrocyte-specific genes including thyroid transcription factor 1 (TTF1), TTF2, paired box gene 8, thyroid stimulating hormone receptor, and sodium/iodide symporter.
conclusionsHesperetin activates the Notch1 signaling cascade and suppresses ATC cell proliferation mainly via apoptosis. Hesperetin also induces cell redifferentiation of ATC, which could be useful clinically.
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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 OpenQuestion graph.