ArticleBiochemical pharmacology2014
Fisetin inhibits human melanoma cell growth through direct binding to p70S6K and mTOR: findings from 3-D melanoma skin equivalents and computational modeling.
Article in Biochemical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 64 citations in OpenAlex.
- 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
- Article
- Modulation ofPeerJ · 2025Article
- Aspirin-Fisetin Combinatorial Treatment Exerts Cytotoxic and Anti-Migratory Activities in A375 Malignant Melanoma Cells.Medicina (Kaunas, Lithuania) · 2024Article
- Article
- Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies.Global medical genetics · 2023Review
- Leveraging Tissue Engineering for Skin Cancer Models.Advances in experimental medicine and biology · 2023Article
- Diet-derived small molecules (nutraceuticals) inhibit cellular proliferation by interfering with key oncogenic pathways: an overview of experimental evidence in cancer chemoprevention.Biologia futura · 2022Review
- Dual targeting of mTOR/IL-17A and autophagy by fisetin alleviates psoriasis-like skin inflammation.Frontiers in immunology · 2022Article
- Current evidence to support the therapeutic potential of flavonoids in oxidative stress-related dermatoses.Redox report : communications in free radical research · 2021Article
- Anti-aging: senolytics or gerostatics (unconventional view).Oncotarget · 2021Review
- Synthesis, inverse docking-assisted identification and in vitro biological characterization of Flavonol-based analogs of fisetin as c-Kit, CDK2 and mTOR inhibitors against melanoma and non-melanoma skin cancers.Bioorganic chemistry · 2021Article
- The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture.Nature communications · 2020Article
- TFEB activates Nrf2 by repressing its E3 ubiquitin ligase DCAF11 and promoting phosphorylation of p62.Scientific reports · 2019Article
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- Article
- Review
- Silencing PDK1 limits hypoxia-induced pulmonary arterial hypertension in mice via the Akt/p70S6K signaling pathway.Experimental and therapeutic medicine · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The incidence of melanoma continues to rise. Inspite of treatment advances, the prognosis remains grim once the disease has metastasized, emphasizing the need to explore additional therapeutic strategies. One such approach is through the use of mechanism-based dietary intervention. We previously showed that the flavonoid fisetin inhibits melanoma cell proliferation, in vitro and in vivo. Here, we studied fisetin-mediated regulation of kinases involved in melanoma growth and progression. Time-course analysis in 3-D melanoma constructs that transitioned from radial to vertical growth showed that fisetin treatment resulted in significant decrease in melanocytic lesions in contrast to untreated controls that showed large tumor nests and invading disseminated cells. Further studies in melanoma cultures and mouse xenografts showed that fisetin-mediated growth inhibition was associated with dephosphorylation of AKT, mTOR and p70S6K proteins. In silico modeling indicated direct interaction of fisetin with mTOR and p70S6K with favorable free energy values. These findings were validated by cell-free competition assays that established binding of fisetin to p70S6K and mTOR while little affinity was detected with AKT. Kinase activity studies reflected similar trend with % inhibition observed for p70S6K and mTOR at lower doses than AKT. Our studies characterized, for the first time, the differential interactions of any botanical agent with kinases involved in melanoma growth and demonstrate that fisetin inhibits mTOR and p70S6K through direct binding while the observed inhibitory effect of fisetin on AKT is mediated indirectly, through targeting interrelated 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.