ArticleFrontiers in pharmacology2019
Apigenin Combined With Gefitinib Blocks Autophagy Flux and Induces Apoptotic Cell Death Through Inhibition of HIF-1α, c-Myc, p-EGFR, and Glucose Metabolism in EGFR L858R+T790M-Mutated H1975 Cells.
Article in Frontiers in pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 58 citations in OpenAlex.
- Multi-Target Antitumor Effects of Natural Products and Approved Drug Repurposing in Non-Small Cell Lung Cancer: Advances in Mechanisms, Combination Regimens, Delivery System Optimization, and Clinical Challenges.International journal of molecular sciences · 2026Review
- Targeting GLUTs in Cancer: Mechanisms, Combination Strategies, and Translational Challenges.Current medical science · 2026Review
- Differential Effects of Apigenin on Normal and Squamous Oral Epithelial Cells Reveal Redox-Autophagy Signaling Vulnerabilities in OSCC.International journal of molecular sciences · 2026Article
- Natural compounds for non-small cell lung cancer treatment: focus on the EGFR signaling pathway.Frontiers in pharmacology · 2026Review
- 2-O-Methylmagnolol suppresses oral squamous cell carcinoma progression by targeting c-MYC signaling.Journal of dental sciences · 2026Article
- The Role of Plant-Derived Natural Products as a Regulator of the Tyrosine Kinase Pathway in the Management of Lung Cancer.Current issues in molecular biology · 2025Review
- Flavonoids in the Treatment of Non-small Cell Lung Cancer via Immunomodulation: Progress to Date.Molecular diagnosis & therapy · 2025Review
- Emerging Role of Hypoxia-Inducible Factors (HIFs) in Modulating Autophagy: Perspectives on Cancer Therapy.International journal of molecular sciences · 2025Review
- Traditional Chinese Medicines as Anticancer Agents for Non-Small Cell Lung Cancer with EGFR Mutations: A Review.Drug design, development and therapy · 2025Review
- Medicinal plants as a potential resource for the discovery of novel structures towards cancer drug resistance treatment.Heliyon · 2024Review
- Apigenin: Molecular Mechanisms and Therapeutic Potential against Cancer Spreading.International journal of molecular sciences · 2024Review
- Article
- Cancer metabolism and carcinogenesis.Experimental hematology & oncology · 2024Review
- Significance of flavonoids targeting PI3K/Akt/HIF-1α signaling pathway in therapy-resistant cancer cells - A potential contribution to the predictive, preventive, and personalized medicine.Journal of advanced research · 2024Review
- Application of Polyphenols and Flavonoids in Oncological Therapy.Molecules (Basel, Switzerland) · 2023Review
- Feiyiliu Mixture sensitizes EGFRFrontiers in pharmacology · 2023Article
- The Potential Role of Apigenin in Cancer Prevention and Treatment.Molecules (Basel, Switzerland) · 2022Review
- Regulation of apoptosis, autophagy and ferroptosis by non-coding RNAs in metastatic non-small cell lung cancer (Review).Experimental and therapeutic medicine · 2022Review
- Role of Induced Programmed Cell Death in the Chemopreventive Potential of Apigenin.International journal of molecular sciences · 2022Review
- Role of HIF-1α/ERRα in Enhancing Cancer Cell Metabolism and Promoting Resistance of Endometrial Cancer Cells to Pyroptosis.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells are characterized by abnormally increased glucose uptake and active bio-energy and biosynthesis to support the proliferation, metastasis, and drug resistant survival. We examined the therapeutic value of the combination of apigenin (a natural small-molecule inhibitor of Glut1 belonging to the flavonoid family) and gefitinib on epidermal growth factor receptor (EGFR)-resistant mutant non-small cell lung cancer, to notably damage glucose utilization and thus suppress cell growth and malignant behavior. Here, we demonstrate that apigenin combined with gefitinib inhibits multiple oncogenic drivers such as c-Myc, HIF-1α, and EGFR, reduces Gluts and MCT1 protein expression, and inactivates the 5' adenosine monophosphate-activated protein kinase (AMPK) signaling, which regulates glucose uptake and maintains energy metabolism, leading to impaired energy utilization in EGFR L858R-T790M-mutated H1975 lung cancer cells. H1975 cells exhibit dysregulated metabolism and apoptotic cell death following treatment with apigenin + gefitinib. Therefore, the combined apigenin + gefitinib treatment presents an attractive strategy as alternative treatment for the acquired resistance to EGFR-TKIs in NSCLC.
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