ArticleJournal of the Egyptian National Cancer Institute2023
In vitro synergistic effect of hesperidin and doxorubicin downregulates epithelial-mesenchymal transition in highly metastatic breast cancer cells.
Article in Journal of the Egyptian National Cancer Institute, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Fenugreek seed extract-doxorubicin synergy against hepatocellular carcinoma in HepG2 cells: in vitro and in silico mechanistic studies.BMC complementary medicine and therapies · 2026Article
- Hesperidin: A Multifunctional Flavonoid with Therapeutic Potential in the Management of Pathogenesis.International journal of molecular sciences · 2026Review
- Article
- Review
- Flavonoid-Based Combination Therapies and Nano-Formulations: An Emerging Frontier in Breast Cancer Treatment.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Traditional Chinese medicine in the treatment of breast Cancer.Molecular cancer · 2025Review
- Exploring the Therapeutic Potential of Oxo berberine Compound in Arcangelisia flava Root Extract for Breast Cancer Treatment: Metabolite Profiling, Pharmacological Network Analysis, and In Silico and In Vitro Evaluation.Asian Pacific journal of cancer prevention : APJCP · 2025Article
- Molecular Mechanisms of Dietary Compounds in Cancer Stem Cells from Solid Tumors: Insights into Colorectal, Breast, and Prostate Cancer.International journal of molecular sciences · 2025Review
- Targeting colorectal cancer with hesperidin and hesperetin: a comprehensive review of antiproliferative activity, chemopreventive, anti-inflammatory, and antioxidant effects.Frontiers in nutrition · 2025Review
- Hesperidin and Diosmin Increased Cytotoxic Activity Cisplatin on Hepatocellular Carcinoma and Protect Kidney Cells Senescence.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Review
- Hesperidin Nanoformulation: A Potential Strategy for Reducing Doxorubicin-Induced Renal Damage via the Sirt-1/HIF1-α/VEGF/NF-κB Signaling Cascade.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Article
- Synergistic therapeutic approach for hemorrhoids: integrating mesenchymal stem cells with diosmin-hesperidin to target tissue edema and inflammation.Archives of medical science : AMS · 2024Article
- Unveiling Paclitaxel-Induced Mesenchymal Stem Cells: orchestrating Nrf2 Modulation and Apoptosis in CD44+/CD24- Cancer Stem Cells.Breast cancer (Dove Medical Press) · 2024Article
- NovelJournal of enzyme inhibition and medicinal chemistry · 2023Article
- The Potential of Eleutherine bulbosa in Inducing Apoptosis and Inhibiting Cell Cycle in Breast Cancer: A Network Pharmacology Approach and In Vitro Experiments.Asian Pacific journal of cancer prevention : APJCP · 2023Review
- Natural-Product-Derived Adjunctive Treatments to Conventional Therapy and Their Immunoregulatory Activities in Triple-Negative Breast Cancer.Molecules (Basel, Switzerland) · 2023Review
- Hesperidin increases theJournal of advanced pharmaceutical technology & researchArticle
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe previously reported that in highly metastatic breast cancer cells, doxorubicin (DOX) at non-toxic concentrations promoted cell migration and invasion. Hesperidin (30, 5, 9-dihydroxy-40-methoxy-7-orutinosyl flavanone) is a flavonoid glycoside isolated from citrus/lemon plant that possesses a cytotoxic effect in several cancer cells. In this study, we investigate whether DOX efficacy is enhanced by hesperidin (Hsd) and the molecular pathway involved in highly metastatic breast cancer, 4T1.
methodsCombined cytotoxicity of Hsd and DOX was evaluated with MTT assay and was analyzed using Chou-Talalay's method. To better understand the underlying mechanism, several factors, including apoptosis and cell cycle arrest were analyzed by flow cytometry. In addition, antimigration activity was evaluated by scratch wound healing assay, MMP-9 expression by ELISA and gelatin zymography, and Rac-1 protein level using western blot. The data on survival rate and expression level of MMP-9 and Rac-1 were obtained from Gene Expression OMNIBUS (GEO).
resultsUnder MTT assay, Hsd showed a cytotoxic effect in a concentration-dependent manner with an IC50 value of 284 µM on 4T1 cells. Hsd synergistically enhanced the cytotoxic effect of DOX which seemed to correlate with an increase in apoptotic cell death, G2/M cell cycle arrest and blocked the migration of 4T1 cells. At 10 nM, doxorubicin induced lamellipodia formation, and increased the level of Rac-1 and metalloproteinase-9 (MMP-9) expression. Interestingly, combined treatment of DOX and Hsd dramatically downregulated the expression of MMP-9 and Rac-1. These results indicated that Hsd block the cell migration induced by DOX under in vitro studies.
conclusionThese findings strongly suggest that Hsd possesses a potential synergistic effect that can be developed to enhance the anticancer efficacy of DOX and reduce the risks of chemotherapy use in highly metastatic breast cancer.
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