ArticleBMC pharmacology & toxicology2019
Apigenin and hesperidin augment the toxic effect of doxorubicin against HepG2 cells.
Article in BMC pharmacology & toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- Combination Chemotherapy with Selected Polyphenols in Preclinical and Clinical Studies-An Update Overview.Molecules (Basel, Switzerland) · 2023Pooled it
- Natural products targeting glycolysis in cancer.Frontiers in pharmacology · 2022Pooled it
- Natural Product Driven Activation of UCP1 and Tumor Metabolic Suppression: Integrating Thermogenic Nutrient Competition with Cancer Metabolic Reprogramming.Biomolecules · 2026Review
- Therapeutic potential and molecular mechanisms of citrus flavonoids in hepatocellular carcinoma.Frontiers in pharmacology · 2026Review
- The glycolysis-lactylation axis: a metabolic-epigenetic driver of immunosuppression and therapy resistance in cancer.Frontiers in immunology · 2026Review
- Article
- The Interventional Effects and Mechanisms of Lonidamine in Combination with Apigenin on Colorectal Cancer.Current issues in molecular biology · 2025Article
- Combined Hesperidin and Doxorubicin Treatment Induces Apoptosis and Modulates Inflammatory Cytokines in HeLa Cervical Cancer Cells.International journal of molecular sciences · 2025Article
- Doxorubicin-Induced Cardiotoxicity: A Comprehensive Update.Journal of cardiovascular development and disease · 2025Review
- Exploratory Analysis of Molecular Subtypes in Early-Stage Osteosarcoma: Identifying Resistance and Optimizing Therapy.Cancers · 2025Article
- A Review on Nanotechnologically Derived Phytomedicines for the Treatment of Hepatocellular Carcinoma: Recent Advances in Molecular Mechanism and Drug Targeting.Current drug targets · 2025Review
- Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer.Molecular cancer · 2024Review
- Autophagy-induced cell death by aqueous and polyphenol-enriched extracts of honeybush (Food science & nutrition · 2024Article
- Mitochondrial uncoupling proteins protect human airway epithelial ciliated cells from oxidative damage.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Natural Product-Based Glycolysis Inhibitors as a Therapeutic Strategy for Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer.International journal of molecular sciences · 2024Review
- Article
- Article
- Critical Review in Designing Plant-Based Anticancer Nanoparticles against Hepatocellular Carcinoma.Pharmaceutics · 2023Review
- Article
- In vitro synergistic effect of hesperidin and doxorubicin downregulates epithelial-mesenchymal transition in highly metastatic breast cancer cells.Journal of the Egyptian National Cancer Institute · 2023Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatocellular carcinoma (HCC) is one of the most common malignancies, with an increasing incidence. Despite the fact that systematic chemotherapy with a doxorubicin provides only marginal improvements in survival of the HCC patients, the doxorubicin is being used in transarterial therapies or combined with the target drug - sorafenib. The aim of the study was to evaluate the effect of natural flavonoids on the cytotoxicity of the doxorubicin against human hepatocellular carcinoma cell line HepG2.
methodsThe effect of apigenin and its glycosides - cosmosiin, rhoifolin; baicalein and its glycosides - baicalin as well as hesperetin and its glycosides - hesperidin on glycolytic genes expression of HepG2 cell line, morphology and cells' viability at the presence of doxorubicin have been tested. In an attempt to elucidate the mechanism of observed results, the fluorogenic probe for reactive oxygen species (ROS), the DNA oxidative damage, the lipid peroxidation and the double strand breaks were evaluated. To assess impact on the glycolysis pathway, the mRNA expression for a hexokinase 2 (HK2) and a lactate dehydrogenase A (LDHA) enzymes were measured. The results were analysed statistically with the one-way analysis of variance (ANOVA) and post hoc multiple comparisons.
resultsThe apigenin and the hesperidin revealed the strongest effect on the toxicity of doxorubicin. Both flavonoids simultaneously changed the expression of the glycolytic pathway genes - HK2 and LDHA, which play a key role in the Warburg effect. Although separate treatment with doxorubicin, apigenin and hesperidin led to a significant oxidative DNA damage and double strand breaks, simultaneous administration of doxorubicin and apigenin or hesperidin abolished these damage with the simultaneous increase in the doxorubicin toxicity.
conclusionThe obtained results indicate the existence of a very effective cytotoxic mechanism in the HepG2 cells of the combined effect of doxorubicin and apigenin (or hesperidin), not related to the oxidative stress. To explain this synergy mechanism, further research is needed, The observed intensification of the cytotoxic effect of doxorubicin by this flavonoids may be a promising direction of the research on the therapy of hepatocellular carcinoma, especially in a chemoembolization.
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