ArticleJournal of experimental & clinical cancer research : CR2020
Formononetin inhibits tumor growth by suppression of EGFR-Akt-Mcl-1 axis in non-small cell lung cancer.
Article in Journal of experimental & clinical cancer research : CR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 62 citations in OpenAlex.
- Formononetin as a potential therapeutic agent for asthma: evidence from in vivo and in vitro models of attenuated inflammation via cAMP/PKA pathway inhibition.In vitro cellular & developmental biology. Animal · 2026Article
- Natural bioactive molecules and chemotherapeutics synergism for enhanced cancer therapy.Nutrition & metabolism · 2026Review
- Dauricine Overcomes Osimertinib Resistance in Lung Cancer by Inducing Ferroptosis via Stabilizing SAT1.Cancer science · 2025Article
- 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
- Research Progress on the Structure-activity Relationship and Mechanism of Flavonoid Derivatives in the Treatment of Lung Cancer.Molecules (Basel, Switzerland) · 2025Review
- Integrated multi-omic high-throughput strategies across-species identified potential key diagnostic, prognostic, and therapeutic targets for atherosclerosis under high glucose conditions.Molecular and cellular biochemistry · 2025Article
- Antitumor activity of afatinib in EGFR T790M-negative human oral cancer therapeutically targets mTOR/Mcl-1 signaling axis.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Extraction, content determination, component analysis, and pharmacological action of Hedysari flavonoids: a review of research progress.Frontiers in pharmacology · 2025Review
- Formononetin: a review of its source, pharmacology, drug combination, toxicity, derivatives, and drug delivery systems.Frontiers in pharmacology · 2025Review
- Recent Applications of In Silico Approaches for Studying Receptor Mutations Associated with Human Pathologies.Molecules (Basel, Switzerland) · 2024Review
- Therapeutic targets of formononetin for treating prostate cancer at the single-cell level.Aging · 2024Article
- Pan-EGFR Inhibitor Dacomitinib Resensitizes Paclitaxel and Induces Apoptosis via Elevating Intracellular ROS Levels in Ovarian Cancer SKOV3-TR Cells.Molecules (Basel, Switzerland) · 2024Article
- Formononetin triggers ferroptosis in triple-negative breast cancer cells by regulating the mTORC1/SREBP1/SCD1 pathway.Frontiers in pharmacology · 2024Article
- Enhancement of the Sensitivity of the Acute Lymphoblastic Leukemia Cells to ABT-737 by Formononetin.International journal of molecular and cellular medicine · 2024Article
- A war on many fronts: cross disciplinary approaches for novel cancer treatment strategies.Frontiers in genetics · 2024Review
- Enhancing Anticancer Efficacy of Formononetin Microspheres via Microfluidic Fabrication.AAPS PharmSciTech · 2023Article
- Anticancer Potential of Flavonoids: An Overview with an Emphasis on Tangeretin.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Potential Therapeutic Targets of Formononetin, a Type of Methoxylated Isoflavone, and Its Role in Cancer Therapy through the Modulation of Signal Transduction Pathways.International journal of molecular sciences · 2023Review
- Exploration of the Use of Natural Compounds in Combination with Chemotherapy Drugs for Tumor Treatment.Molecules (Basel, Switzerland) · 2023Review
Corrections and comments
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Authors and funding
6 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundEpidermal growth factor receptor (EGFR) activating mutations play crucial roles in the tumorigenesis of human non-small cell lung cancer (NSCLC). The mechanism regarding how EGFR signaling regulates myeloid cell leukemia sequence 1 (Mcl-1) protein stability and ubiquitination remains undefined.
methodsMTS assay was used for natural product library screening. The effect of formononetin (Formo) on NSCLC cells was determined by MTS assay and soft agar assay. Molecular modeling was performed to analyze the potential different binding modes between Formo and EGFR WT or mutants. Mcl-1 protein level and the inhibitory effect of Formo on EGFR signaling were examined by immunoblot, in vitro kinase assay, in vitro pulldown and ATP competition assays, co-immunoprecipitation assay, ubiquitination analysis, in vivo xenograft model, and immunohistochemical staining.
resultsFormo was identified as an EGFR inhibitor by a 98 commercially available natural product screening. Formo suppresses WT and mutant EGFR kinases activity in vitro, ex vivo, and in vivo. Molecular modeling indicates that Formo docks into the ATP-binding pocket of both WT and mutant EGFR. Formo inhibits EGFR-Akt signaling, which in turn activates GSK3β and promotes Mcl-1 phosphorylation in NSCLC cells. Treatment with Formo enhances the interaction between Mcl-1 and SCF
conclusionThis study highlights the importance of promoting ubiquitination-dependent Mcl-1 turnover might be an alternative strategy to enhance the anti-tumor efficacy of EGFR-TKI.
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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.