ArticleBritish journal of cancer2017
Genistein suppresses aerobic glycolysis and induces hepatocellular carcinoma cell death.
Article in British journal of cancer, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.
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Who cites it
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 citations in OpenAlex.
- Natural products targeting glycolysis in cancer.Frontiers in pharmacology · 2022Pooled it
- Genistein and Butein as Bioactive Polyphenols: Molecular Targets, Metabolic Regulation, and Mechanistic Insights.Life (Basel, Switzerland) · 2026Review
- The moonlighting functions of glycolytic enzymes in tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Metabolic reprogramming-driven resistance to multi-kinase inhibitors in hepatocellular carcinoma: molecular mechanisms and therapeutic opportunities.Molecular cancer · 2026Review
- Pyruvate kinase M2 in Alzheimer's disease: from dysregulation to therapeutic inhibition.Brain communications · 2026Review
- Exosome-Mediated Regulation of Aerobic Glycolysis in Hepatocellular Carcinoma: Mechanisms and Therapeutic Implications.Journal of hepatocellular carcinoma · 2026Review
- Metabolic Reprogramming-Targeted Therapeutic Strategies in Primary Liver Cancer: A Bibliometric and Visualized Analysis.Journal of hepatocellular carcinoma · 2026Article
- Beyond the convergence of metabolic reprogramming in primary liver cancer: a comprehensive review on energy and lipids metabolism.Frontiers in cell and developmental biology · 2026Review
- Leucyl-tRNA synthetase promotes malignant progression in diffuse large B-cell lymphoma by regulating glycolysis via the LRPPRC/HIF-1α/HK2 axis.Human cell · 2025Article
- Phytochemicals in Cancer Therapy: A Structured Review of Mechanisms, Challenges, and Progress in Personalized Treatment.Chemistry & biodiversity · 2025Review
- The role of proteomics and radioproteomics in biomarkers of liver HCC for diagnosis, therapy and enhance interventional radiological treatments.Cancer reports and reviews · 2025Article
- Lactylation: From Molecular Insights to Disease Relevance.Biomolecules · 2025Review
- Genistein in focus: pharmacological effects and immune pathway modulation in cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Carvacrol potentiates immunity and sorafenib anti-cancer efficacy by targeting HIF-1α/STAT3/ FGL1 pathway: in silico and in vivo study.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Progress of research on glucose transporter proteins in hepatocellular carcinoma.World journal of hepatology · 2025Review
- Soy Isoflavone Genistein Enhances Tamoxifen Sensitivity in Breast Cancer via microRNA and Glucose Metabolism Modulation.International journal of molecular sciences · 2025Article
- Dihydroartemisinin: A Promising Therapeutic Agent Against the Hepatitis-to-Hepatocellular Carcinoma Cascade.Drug design, development and therapy · 2025Review
- The Role of HK2 in Tumorigenesis and Development: Potential for Targeted Therapy with Natural Products.International journal of medical sciences · 2025Review
- Genetic Variants ofJournal of hepatocellular carcinoma · 2025Article
- Polydatin-Induced Shift of Redox Balance and Its Anti-Cancer Impact on Human Osteosarcoma Cells.Current issues in molecular biology · 2024Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGenistein is a natural isoflavone with many health benefits, including antitumour effects. Increased hypoxia-inducible factor 1 α (HIF-1α) levels and glycolysis in tumour cells are associated with an increased risk of mortality, cancer progression, and resistance to therapy. However, the effect of genistein on HIF-1α and glycolysis in hepatocellular carcinoma (HCC) is still unclear.
methodsCell viability, apoptosis rate, lactate production, and glucose uptake were measured in HCC cell lines with genistein incubation. Lentivirus-expressed glucose transporter 1 (GLUT1) or/and hexokinase 2 (HK2) and siRNA of HIF-1α were used to test the direct target of genistein. Subcutaneous xenograft mouse models were used to measure in vivo efficacy of genistein and its combination with sorafenib.
resultsGenistein inhibited aerobic glycolysis and induced mitochondrial apoptosis in HCC cells. Neither inhibitors nor overexpression of HK2 or GLUTs enhance or alleviate this effect. Although stabiliser of HIF-1α reversed the effect of genistein, genistein no longer has effects on HIF-1α siRNA knockdown HCC cells. In addition, genistein enhanced the antitumour effect of sorafenib in sorafenib-resistant HCC cells and HCC-bearing mice.
conclusionsGenistein sensitised aerobic glycolytic HCC cells to apoptosis by directly downregulating HIF-1α, therefore inactivating GLUT1 and HK2 to suppress aerobic glycolysis. The inhibitory effect of genistein on tumour cell growth and glycolysis may help identify effective treatments for HCC patients at advanced stages.
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Registered trials
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.