Prostate cancer is one of the most common cancers in men, and its slow growth makes it an attractive target for anything taken by mouth over years. Fisetin has a long laboratory record against it, starting with a 2008 study that found it killed prostate cancer cells while barely affecting normal prostate cells [1].
A 2021 systematic review counted 15 preclinical papers on fisetin in prostate or bladder cancer, with much more limited evidence from animals, population studies or trials, and concluded that the work justifies clinical trials [2]. That is the honest status: a strong case for testing, and no test in men yet. This page goes through the studies and what they cannot tell you.
Key Takeaways
- At 10 to 60 micromolar, fisetin reduced the viability of three prostate cancer cell lines with minimal effect on normal prostate epithelial cells [1].
- It blocked mTOR signalling in hormone-resistant PC3 cells and bound to tubulin, the target of taxane chemotherapy [3][4].
- With the chemotherapy drug cabazitaxel, it reduced tumour growth and spread in two mouse models [5].
- No clinical trial has tested fisetin in men with prostate cancer, and none of these studies measured PSA or looked at benign prostate enlargement.
Important: This article describes laboratory research and is not medical advice. If you have prostate cancer, or are on hormone therapy, chemotherapy or active surveillance, do not take fisetin without your urologist or oncologist. Its effects on PSA readings and on prostate cancer drugs have not been studied in men, and it can affect drug-metabolising enzymes.
The first studies: cell death and the cell cycle
The 2008 study treated three human prostate cancer lines, LNCaP, CWR22Rv1 and PC-3, with fisetin at 10 to 60 micromolar for 48 hours. Viability fell in all three, with only minimal effects on normal prostate epithelial cells [1]. In LNCaP cells, fisetin stopped the cell cycle in G1 by lowering cyclins and their partner kinases, and triggered apoptosis through the mitochondria, with activation of caspases 3, 8 and 9. Blocking caspases blocked that activation.
A 2010 study turned to PC-3 cells, a highly metastatic line. At concentrations that did not kill the cells, fisetin reduced their ability to stick, migrate and invade [6]. It lowered MMP-2 and MMP-9, enzymes that cancer cells use to break through surrounding tissue, by suppressing PI3K/Akt and JNK signalling. Our page on fisetin in preclinical cancer research covers the same mechanisms in other cancers.
Hormone-resistant cells and mTOR
Most prostate cancers depend on male hormones at first and are treated by lowering them. Many eventually stop responding, becoming castration-resistant. PC3 cells are a model of that stage: androgen-independent and missing the tumour suppressor PTEN. In PC3 cells, fisetin inhibited mTOR, broke up both mTOR complexes and triggered autophagic cell death rather than the protective kind of autophagy [3].
The research group behind much of this work summarised it in 2012, describing fisetin as a dual inhibitor of the PI3K/Akt and mTOR pathways in prostate and lung cancer cells [7]. Dual inhibitors of those pathways have been suggested as valuable agents for such cancers, which is why the finding attracted attention.
Flavonols as a group have also been proposed to act on the androgen receptor, through 5-alpha reductase inhibition, competition with androgens and other routes. A 2015 review of quercetin, myricetin, kaempferol and fisetin concluded that it is still unclear whether those effects explain their activity in prostate cancer [8]. For the separate question of fisetin and testosterone in healthy men, see our page on fisetin, testosterone and male fertility.
Tubulin and cabazitaxel
Taxanes such as docetaxel and cabazitaxel work by locking the cell’s internal scaffolding, the microtubules, so the cell cannot divide. A 2015 study found fisetin binds beta-tubulin and stabilises microtubules, and on surface plasmon resonance and computer docking it bound with higher affinity than paclitaxel [4]. Binding affinity is not potency as a drug, and the authors call their result an in vitro proof of concept. Fisetin reduced prostate cancer cell proliferation, migration and invasion, and reduced viability in a multidrug-resistant cell line.
The same group then combined fisetin at 20 micromolar with cabazitaxel at 5 nanomolar. The pair worked synergistically against three prostate cancer lines, with minimal harm to normal prostate epithelial cells, and in two xenograft mouse models it inhibited tumour growth, invasion and metastasis [5]. The authors suggest fisetin might let cabazitaxel work at lower, less toxic doses. That has not been tested in men, and adding a supplement to chemotherapy without the oncologist can change how the drugs behave; our page on fisetin and chemotherapy timing covers that question.
Hyaluronan and the TRAMP mouse
A 2016 study searched for what fisetin changes in prostate tumours. In tumours from treated animals, hyaluronan, a large sugar molecule in the tissue around cells, was the most affected metabolite [9]. In cells and in TRAMP mice, a strain that develops prostate cancer on its own, fisetin lowered hyaluronan levels and shifted what was left towards the long, high-molecular-mass form, which is anti-inflammatory and restrains growth signalling, and away from the short form, which promotes it.
The dose gap and the missing trials
The concentrations in these studies are high. With fisetin’s molecular weight of about 286.24 g/mol, 10 micromolar is about 2,862 ng/mL and the 20 micromolar used with cabazitaxel is about 5,725 ng/mL. In healthy volunteers, a single 1,000 mg dose of plain fisetin peaked at 9.97 ng/mL and a formulated version at 238.2 ng/mL [10]. Even the formulated peak is roughly 12 times below the lowest concentration in the 2008 study. Tissue levels in the prostate have not been measured.
The idea of testing fisetin in patients has reached the clinical literature. A 2022 editorial in Future Science OA argued for fisetin as an add-on treatment for men receiving androgen-deprivation therapy [11]. An editorial is an argument, not data. The 2021 systematic review reached the same place more formally: the preclinical evidence and expected low toxicity justify trials that work out dosing and clinical settings [2].
There are also gaps that matter to men making a decision today. None of the studies here measured PSA, the blood test used to monitor prostate cancer, and none looked at benign prostate enlargement or urinary symptoms. If you are being monitored, tell your doctor about any supplement so that a change in PSA can be interpreted correctly. For dosing and safety in general, see our fisetin dosage guide and fisetin side effects overview.
Common questions
Does fisetin help prostate cancer?
In prostate cancer cells and mouse models, yes [1][5]. It has not been tested in men with prostate cancer, so there is no evidence it helps patients.
Does fisetin work on hormone-resistant prostate cancer?
In androgen-independent PC3 cells it blocked mTOR signalling and triggered autophagic cell death [3]. That is a cell result, not a clinical one.
Can fisetin be taken with cabazitaxel or other chemotherapy?
Only with your oncologist. The combination with cabazitaxel worked in cells and mice [5], but it has not been tested in patients.
Does fisetin lower PSA?
No study has measured fisetin’s effect on PSA in men. Tell your doctor about any supplement you take while being monitored.
Does fisetin help an enlarged prostate (BPH)?
There is no research on fisetin for benign prostate enlargement. The studies here are on prostate cancer cells and mice.
References
- Fisetin, a novel dietary flavonoid, causes apoptosis and cell cycle arrest in human prostate cancer LNCaP cells. Carcinogenesis (2008). PMID 18359761
- Kaempferol, Myricetin and Fisetin in Prostate and Bladder Cancer: A Systematic Review of the Literature. Nutrients (2021). PMID 34836005
- Fisetin induces autophagic cell death through suppression of mTOR signaling pathway in prostate cancer cells. Carcinogenesis (2010). PMID 20530556
- Dietary flavonoid fisetin binds to beta-tubulin and disrupts microtubule dynamics in prostate cancer cells. Cancer Lett (2015). PMID 26235140
- Fisetin Enhances Chemotherapeutic Effect of Cabazitaxel against Human Prostate Cancer Cells. Mol Cancer Ther (2016). PMID 27765854
- Antimetastatic potential of fisetin involves inactivation of the PI3K/Akt and JNK signaling pathways with downregulation of MMP-2/9 expressions in prostate cancer PC-3 cells. Mol Cell Biochem (2010). PMID 19633975
- Dietary flavonoid fisetin: a novel dual inhibitor of PI3K/Akt and mTOR for prostate cancer management. Biochem Pharmacol (2012). PMID 22842629
- Anti-androgenic effects of flavonols in prostate cancer. Ecancermedicalscience (2015). PMID 26557883
- Dietary flavonoid fisetin increases abundance of high-molecular-mass hyaluronan conferring resistance to prostate oncogenesis. Carcinogenesis (2016). PMID 27335141
- 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 as an adjuvant treatment in prostate cancer patients receiving androgen-deprivation therapy. Future Sci OA (2022). PMID 35251698
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.