ArticlePloS one2014
Fisetin inhibits human melanoma cell invasion through promotion of mesenchymal to epithelial transition and by targeting MAPK and NFκB signaling pathways.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 47 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
47 citing papers in PubMed, 105 citations in OpenAlex.
- Targeting MAPK Pathways in Skin, Thyroid, and Pancreatic Cancer: A Perspective on Synthetic Inhibitors and Natural Modulators.Advanced biology · 2026Review
- Fisetin: a multitarget flavonol bridging oxidative stress, inflammation, aging, and cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Fisetin as a chemoprotective and chemotherapeutic agent: mechanistic insights and future directions in cancer therapy.Medical oncology (Northwood, London, England) · 2025Review
- Natural products as therapeutics for malignant melanoma: preclinical evidence and mechanism.Frontiers in pharmacology · 2025Review
- Review
- Aspirin-Fisetin Combinatorial Treatment Exerts Cytotoxic and Anti-Migratory Activities in A375 Malignant Melanoma Cells.Medicina (Kaunas, Lithuania) · 2024Article
- Combined therapy of dabrafenib and an anti-HER2 antibody-drug conjugate for advanced BRAF-mutant melanoma.Cellular & molecular biology letters · 2024Article
- Article
- The Promising Role of Polyphenols in Skin Disorders.Molecules (Basel, Switzerland) · 2024Review
- Article
- Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies.Global medical genetics · 2023Review
- Biological effects and mechanisms of fisetin in cancer: a promising anti-cancer agent.European journal of medical research · 2023Review
- Melanoma Cellular Signaling Transduction Pathways Targeted by Polyphenols Action Mechanisms.Antioxidants (Basel, Switzerland) · 2023Review
- Fisetin in Cancer: Attributes, Developmental Aspects, and Nanotherapeutics.Pharmaceuticals (Basel, Switzerland) · 2023Review
- The Potential Role of Fisetin, a Flavonoid in Cancer Prevention and Treatment.Molecules (Basel, Switzerland) · 2022Review
- Identification of Dihydrolipoamide Dehydrogenase as Potential Target of Vemurafenib-Resistant Melanoma Cells.Molecules (Basel, Switzerland) · 2022Article
- Article
- Chemical Structure, Sources and Role of Bioactive Flavonoids in Cancer Prevention: A Review.Plants (Basel, Switzerland) · 2022Review
- Melanization as unfavorable factor in amelanotic melanoma cell biology.Protoplasma · 2021Article
- The Role of Senescent Cells in Acquired Drug Resistance and Secondary Cancer in BRAFi-Treated Melanoma.Cancers · 2021Review
Corrections and comments
- Expression of concern
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Malignant melanoma is responsible for approximately 75% of skin cancer-related deaths. BRAF plays an important role in regulating the mitogen-activated protein kinase (MAPK) signaling cascade in melanoma with activating mutations in the serine/threonine kinase BRAF occurring in 60-70% of malignant melanomas. The BRAF-MEK-ERK (MAPK) pathway is a key regulator of melanoma cell invasion. In addition, activation of NFκB via the MAPK pathway is regulated through MEK-induced activation of IKK. These pathways are potential targets for prevention and treatment of melanoma. In this study, we investigated the effect of fisetin, a phytochemical present in fruits and vegetables, on melanoma cell invasion and epithelial-mesenchymal transition, and delineated the underlying molecular mechanism. Treatment of multiple human malignant melanoma cell lines with fisetin (5-20 µM) resulted in inhibition of cell invasion. BRAF mutated melanoma cells were more sensitive to fisetin treatment, and this was associated with a decrease in the phosphorylation of MEK1/2 and ERK1/2. In addition, fisetin inhibited the activation of IKK leading to a reduction in the activation of the NFκB signaling pathway. Treatment of cells with an inhibitor of MEK1/2 (PD98059) or of NFκB (caffeic acid phenethyl ester) also reduced melanoma cell invasion. Furthermore, treatment of fisetin promoted mesenchymal to epithelial transition in melanoma cells, which was associated with a decrease in mesenchymal markers (N-cadherin, vimentin, snail and fibronectin) and an increase in epithelial markers (E-cadherin and desmoglein). Employing three dimensional skin equivalents consisting of A375 cells admixed with normal human keratinocytes embedded onto a collagen-constricted fibroblast matrix, we found that treatment of fisetin reduced the invasive potential of melanoma cells into the dermis and increased the expression of E-cadherin with a concomitant decrease in vimentin. These results indicate that fisetin inhibits melanoma cell invasion through promotion of mesenchymal to epithelial transition and by targeting MAPK and NFκB signaling pathways.
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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.