Melanoma is the most dangerous common skin cancer, and fisetin has been studied against it repeatedly. A run of laboratory papers shows fisetin slowing melanoma cells, reducing tumours in mice, and adding to the effect of the drug sorafenib [1][2].
None of that work has reached a melanoma patient. There is no published clinical trial of fisetin in melanoma, and the studies below use cancer cell lines, lab-grown skin models and mice carrying human tumours. This page sets out what was found, at what concentrations, and two problems in the wider literature that a careful reader should know about.
Key Takeaways
- In 451Lu melanoma cells and in mice carrying 451Lu tumours, fisetin slowed growth and lowered Mitf, a protein that drives melanoma [1].
- In mice carrying BRAF-mutated human melanoma, fisetin plus sorafenib reduced tumour growth more than either alone [2].
- The cell studies use micromolar concentrations that are many times above the levels measured in the first human pharmacokinetic study of fisetin [3].
- No clinical trial has tested fisetin in people with melanoma. One related paper has been retracted and another carries an expression of concern.
Important: This article describes laboratory research and is not medical advice. If you have melanoma or are being treated for it, do not take fisetin without your oncology team. It has not been tested alongside immunotherapy or targeted melanoma drugs in people, and it can affect drug-metabolising enzymes. Fisetin is not a substitute for sun protection or skin checks.
Melanoma cells: growth, Mitf and mTOR
The foundational study used 451Lu human melanoma cells. Fisetin reduced their viability, held them in the G1 phase of the cell cycle and disrupted Wnt/beta-catenin signalling, a growth pathway that is often switched on in melanoma [1]. Downstream, it lowered Mitf, a master regulator of melanocytes that is used as a prognostic marker in melanoma. In nude mice carrying 451Lu tumours, fisetin inhibited tumour development and lowered Mitf in the tumours.
Follow-up work from the same group looked at growth signalling. In lab-grown 3-D skin models in which melanoma moves from spreading along the surface to invading downward, fisetin-treated models showed significantly fewer melanocytic lesions than untreated ones, which developed large tumour nests and invading cells [4]. Cell-free binding assays showed fisetin binding directly to mTOR and p70S6K, two kinases that drive cell growth, with little affinity for AKT. Our page on fisetin and rapamycin explains why mTOR comes up so often in fisetin research.
How the cells die
In A375 and 451Lu cells, two aggressive metastatic lines, fisetin triggered endoplasmic reticulum stress, a sign the cell’s protein-folding system is overloaded, followed by both the external and internal routes to apoptosis [5]. Sixteen days of fisetin in a 3-D melanoma model inhibited progression, with increased staining for cleaved caspase-3, a marker of apoptosis. The authors concluded that apoptosis is the main way fisetin kills melanoma cells.
Uveal melanoma, which starts in the eye rather than the skin, is a different disease. In cultured uveal melanoma cells, fisetin reduced viability in a dose-dependent way and triggered mitochondrial apoptosis, while the viability of normal retinal pigment epithelial cells was not affected [6]. That selectivity is encouraging but was shown only in culture. For the general picture across cancer types, see our page on fisetin in preclinical cancer research.
Fisetin alongside melanoma drugs
Many melanomas carry a BRAF mutation, which keeps a growth pathway permanently on. Sorafenib is an older RAF inhibitor. In BRAF-mutated human melanoma cells, fisetin plus sorafenib reduced growth at lower doses than either agent alone, and increased apoptosis [2]. In nude mice carrying A375 or SK-MEL-28 tumours, the combination reduced tumour growth more than either drug alone.
A companion study looked at spread. The combination reduced migration and invasion of BRAF-mutated cells more than either agent, and in mice injected intravenously with A375 cells it produced fewer lung metastases than monotherapy [7]. A 2018 study reported that fisetin binds the kinase RSK, more strongly RSK2 than RSK1, and in this study’s models fisetin and the BRAF drug vemurafenib inhibited melanoma growth to a comparable degree, through different effects on ERK signalling [8].
A 2024 study combined fisetin with aspirin. In A375 cells, aspirin at 2.5 mM plus fisetin at 5 to 20 micromolar was more cytotoxic than either alone and reduced migration [9]. The combination did not irritate a chicken egg membrane and reduced blood vessel growth on it. That egg test screens for irritation and angiogenesis; it is not a melanoma model.
None of these combinations has been tested in a patient. Standard melanoma care now relies heavily on immunotherapy and newer BRAF and MEK inhibitors, and no study has looked at fisetin alongside them in people. Our page on fisetin and chemotherapy timing covers why combining supplements with cancer treatment needs an oncologist.
The concentration problem
Cell studies use micromolar concentrations; human studies measure nanograms per millilitre of plasma. Fisetin’s molecular weight is about 286.24 g/mol, so 20 micromolar, the top concentration in the aspirin study, is about 5,725 ng/mL. In healthy volunteers, a single 1,000 mg dose of plain fisetin produced a peak plasma level of 9.97 ng/mL, and a formulated version 238.2 ng/mL [3]. 20 micromolar is roughly 24 times the formulated peak and roughly 574 times the plain one.
Researchers know this. A 2023 study packaged fisetin in nanostructured lipid carriers to improve delivery. In A-375 and B16F10 melanoma cells, the carriers lowered the concentration needed to kill half the cells by at least about 3.2 times and raised uptake about 1.8 times compared with plain fisetin [10]. In mice, the authors report 5.9-fold and 10.7-fold higher inhibition of metastasis to the lungs and liver; the abstract does not spell out the comparison group. Our page on why fisetin absorbs poorly explains the underlying problem, and the formulations guide covers what is on the market.
Two problems in the wider literature
Anyone searching this topic will find a 2020 paper reporting that fisetin increased melanin production in mouse melanoma cells and zebrafish larvae. That paper has been retracted by its journal, and it is not cited here. A 2025 study reported the opposite direction: in human melanoma cells, fisetin up to 60 micromolar was not toxic and reduced tyrosinase activity and melanin content [11]. That is a pigmentation finding, relevant to dark spots, not to melanoma treatment.
A 2014 study on fisetin and melanoma cell invasion now carries a formal expression of concern from its journal, published in 2024. It is also not cited here. Neither notice changes the other findings above, which come from separate papers, but they are a reminder that a single cell study is a weak foundation for a health decision.
For fisetin’s effects on ageing skin rather than skin cancer, see our page on fisetin and skin aging.
Common questions
Can fisetin treat melanoma?
It has not been tested in people with melanoma. In cells and in mice carrying human melanoma tumours, it slowed growth [1], and with sorafenib it reduced tumour growth more than either alone [2].
Does fisetin prevent melanoma?
There is no human evidence that it does. The studies use cancer cells and mice with implanted tumours, not people at risk of melanoma.
Can I take fisetin during melanoma treatment?
Only with your oncology team’s agreement. Fisetin has not been studied alongside immunotherapy or current targeted melanoma drugs in people.
Does fisetin affect skin pigment?
A 2025 cell study found it lowered tyrosinase activity and melanin in human melanoma cells [11]. A 2020 paper claiming the opposite has been retracted.
Are the concentrations in these studies realistic?
Not from a standard capsule. 20 micromolar is about 5,725 ng/mL, while the formulated peak in the first human pharmacokinetic study was 238.2 ng/mL [3].
References
- Inhibition of human melanoma cell growth by the dietary flavonoid fisetin is associated with disruption of Wnt/beta-catenin signaling and decreased Mitf levels. J Invest Dermatol (2011). PMID 21346776
- Fisetin, a phytochemical, potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells. Oncotarget (2015). PMID 26299806
- Enhanced bioavailability and pharmacokinetics of a novel hybrid-hydrogel formulation of fisetin orally administered in healthy individuals: a randomised double-blinded comparative crossover study. J Nutr Sci (2022). PMID 36304817
- Fisetin inhibits human melanoma cell growth through direct binding to p70S6K and mTOR: findings from 3-D melanoma skin equivalents and computational modeling. Biochem Pharmacol (2014). PMID 24675012
- Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma. Arch Biochem Biophys (2014). PMID 25016296
- Fisetin induces apoptosis through mitochondrial apoptosis pathway in human uveal melanoma cells. Environ Toxicol (2018). PMID 29383865
- Fisetin, a dietary flavonoid, augments the anti-invasive and anti-metastatic potential of sorafenib in melanoma. Oncotarget (2016). PMID 26517521
- Fisetin targets YB-1/RSK axis independent of its effect on ERK signaling: insights from in vitro and in vivo melanoma models. Sci Rep (2018). PMID 30356079
- Aspirin-Fisetin Combinatorial Treatment Exerts Cytotoxic and Anti-Migratory Activities in A375 Malignant Melanoma Cells. Medicina (Kaunas) (2024). PMID 39064554
- Fisetin-Loaded Nanostructured Lipid Carriers: Formulation and Evaluations against Advanced and Metastatic Melanoma. Mol Pharm (2023). PMID 37906601
- Mechanistic Insights into Anti-Melanogenic Effects of Fisetin: PKCalpha-Induced beta-Catenin Degradation, ERK/MITF Inhibition, and Direct Tyrosinase Suppression. Int J Mol Sci (2025). PMID 41373883
These statements have not been evaluated by the Food and Drug Administration. This information is not intended to diagnose, treat, cure, or prevent any disease. Content is for informational purposes only and is not medical advice; consult a qualified healthcare provider before starting any supplement. As an Amazon Associate we earn from qualifying purchases.