ArticleNeoplasia (New York, N.Y.)2015
Kaempferol Suppresses Transforming Growth Factor-β1-Induced Epithelial-to-Mesenchymal Transition and Migration of A549 Lung Cancer Cells by Inhibiting Akt1-Mediated Phosphorylation of Smad3 at Threonine-179.
Article in Neoplasia (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Antiangiogenic Activity of Flavonoids: A Systematic Review and Meta-Analysis.Molecules (Basel, Switzerland) · 2020Pooled it
- Targeting receptor tyrosine kinases: from molecular mechanisms to clinical therapeutics.Signal transduction and targeted therapy · 2026Review
- Regulatory Roles of Kaempferol on the PI3K/AKT/mTOR Signaling Pathway and Associated MicroRNAs in Different Cancer Types.International journal of molecular sciences · 2026Review
- Extracellular Vesicles fromNanomaterials (Basel, Switzerland) · 2026Article
- Review
- Target identification of natural products in cancer with chemical proteomics and artificial intelligence approaches.Cancer biology & medicine · 2025Review
- Review
- Antitumor Activity of Isalpinin fromMolecules (Basel, Switzerland) · 2025Article
- Kaempferol inhibits oxidative stress and reduces macrophage pyroptosis by activating the NRF2 signaling pathway.PloS one · 2025Article
- Research progress on the anti-cancer mechanisms of edible salty-flavored Chinese materia medica.Frontiers in pharmacology · 2025Review
- A Mesenchymal stem cell Aging Framework, from Mechanisms to Strategies.Stem cell reviews and reports · 2024Review
- Computational analysis of phytocompounds inHeliyon · 2024Article
- Article
- Targeting the key players of phenotypic plasticity in cancer cells by phytochemicals.Cancer metastasis reviews · 2024Review
- Modulation of hypoxia-inducible factor-1 signaling pathways in cancer angiogenesis, invasion, and metastasis by natural compounds: a comprehensive and critical review.Cancer metastasis reviews · 2024Review
- Network pharmacology study to explore the multiple molecular mechanism of SH003 in the treatment of non-small cell lung cancer.BMC complementary medicine and therapies · 2024Article
- The Anticancer Potential of Kaempferol: A Systematic Review Based on In Vitro Studies.Cancers · 2024Review
- Research Progress of Baihe Gujin Decoction in the Treatment of Lung Cancer.Cancer management and research · 2024Review
- Phytochemical analysis and anticancer effect ofFrontiers in pharmacology · 2024Article
- Polyphenols as Therapeutics in Respiratory Diseases: Moving from Preclinical Evidence to Potential Clinical Applications.International journal of biological sciences · 2024Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kaempferol, a natural dietary flavonoid, is well known to possess chemopreventive and therapeutic anticancer efficacy; however, its antimetastatic effects have not been mechanistically studied so far in any cancer model. This study was aimed to investigate the inhibitory effect and accompanying mechanisms of kaempferol on epithelial-to-mesenchymal transition (EMT) and cell migration induced by transforming growth factor-β1 (TGF-β1). In human A549 non-small lung cancer cells, kaempferol strongly blocked the enhancement of cell migration by TGF-β1-induced EMT through recovering the loss of E-cadherin and suppressing the induction of mesenchymal markers as well as the upregulation of TGF-β1-mediated matrix metalloproteinase-2 activity. Interestingly, kaempferol reversed TGF-β1-mediated Snail induction and E-cadherin repression by weakening Smad3 binding to the Snail promoter without affecting its C-terminus phosphorylation, complex formation with Smad4, and nuclear translocation under TGF-β1 stimulation. Mechanism study revealed that the phosphorylation of Smad3 linker region induced by TGF-β1 was required for the induction of EMT and cell migration, and selective downregulation of the phosphorylation of Smad3 at Thr179 residue (not Ser204, Ser208, and Ser213) in the linker region was responsible for the inhibition by kaempferol of TGF-β1-induced EMT and cell migration. Furthermore, Akt1 was required for TGF-β1-mediated induction of EMT and cell migration and directly phosphorylated Smad3 at Thr179, and kaempferol completely abolished TGF-β1-induced Akt1 phosphorylation. In summary, kaempferol blocks TGF-β1-induced EMT and migration of lung cancer cells by inhibiting Akt1-mediated phosphorylation of Smad3 at Thr179 residue, providing the first evidence of a molecular mechanism for the anticancer effect of kaempferol.
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