Fisetin
Fisetin clears senescent cells (caspase-driven), boosts apoptosis (Bax/Bcl-2), inhibits PI3K/Akt/mTOR + NF-κB/STAT3/VEGF for anti-prolif/inflam/angio. Preclinical strong in breast/CRC/lung/prostate; pulsed 100–2000 mg safe but monitor CYP/GI—no human oncology trials yet.
Forms: Oral capsules/powder (supplement, 100–500 mg)
Key Takeaway
Fights cancer by clearing “zombie” senescent cells and pushing tumor cells toward apoptosis while dialing down PI3K/Akt growth signals; evidence is mainly preclinical.
Evidence at a glance
Strong preclinical (in vitro/in vivo); human limited to senolysis pilots (non-onco); cancer trials pending.
How it may work
Fisetin, a flavonoid found in strawberries and apples, acts as a senolytic agent by selectively inducing apoptosis in senescent cells through activation of caspases-8 and -9, clearing 'zombie' cells that promote tumor growth. It inhibits PI3K/Akt/mTOR signaling, reducing proliferation, and upregulates pro-apoptotic proteins like Bax while downregulating anti-apoptotic Bcl-2. Fisetin also suppresses NF-κB and STAT3 pathways, limiting inflammation-driven cancer progression, and inhibits angiogenesis via VEGF downregulation. Preclinical studies demonstrate efficacy in breast, colon, and lung cancer models.
Targets & pathways
Curated mechanistic targets reported for this agent — how it may act on cells, not proof of a clinical effect.
- Senolytic Clearance↑Selective apoptosis in senescent cells via caspases-8/9
- Apoptosis↑Bax ↑, Bcl-2 ↓; mitochondrial pathway
- PI3K/Akt/mTOR↓Reduces proliferation/survival
- NF-κB/STAT3↓Limits inflammation/progression
- VEGF↓Inhibits angiogenesis
Often studied / combined with
Combinations reported in the literature, not a protocol or a recommendation.
- Quercetin: Senolytic/apoptosis in breast.
- Dasatinib: Senescent clearance in lung.
- Curcumin: PI3K/Akt in CRC.
Overlapping mechanisms
- Senolytic / Apoptosis ↑ / PI3K ↓: Avoid stacking with other senolytics/PI3K/apoptotics; risk GI/CYP without proportional gain.
Safety & interactions
Severity and how well-established each signal is are shown separately. Verify everything with your oncologist or pharmacist — absence here does not mean safe.
- CYP450 substrates (e.g., caffeine, warfarin)MonitorModerateTheoreticalFisetin inhibits metabolism; levels may rise.
- PI3K inhibitors (e.g., idelalisib)MonitorModerateTheoreticalAdditive pathway inhibition; tox risk.
- Quercetin / Dasatinib / CurcuminConsiderBeneficialTheoreticalSenolytic/apoptosis/PI3K synergies in breast/lung/CRC.
Timing
- With fatty meal: Enhances bioavailability.
- Pulsed (senolytic): E.g., 2 consecutive days/month.
- Divided doses: BID for >500 mg to minimize GI.
References
Research
No published studies for Fisetin yet
New studies appear here once they’ve been reviewed. Browse all studies.
Dose: as studied, not a recommendation
Ranges seen in adjunct / practice use: 100–2000 mg (po) Dietary: 10–100 mg/day from food. Supplements: 100–500 mg/day continuous; senolytic protocols: 20 mg/kg (~1400 mg for 70 kg) for 2 days, repeated monthly. Preclinical HED from mouse (10–50 mg/kg) ~0.8–4 mg/kg (~56–280 mg daily); human trials explore 100–2000 mg pulsed., Pulsed for senolysis (e.g., 2 days on/month). Take with fat for absorption. Bioavailability moderate; piperine may enhance. Not Rx; monitor GI at high doses..
Trials studying Fisetin
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