Fisetin / NF-kB Cancer Research Results

FIS, Fisetin: Click to Expand ⟱

Features:

Fisetin is a plant based flavonoid. Found in strawberries(160ug/g), apples, persimmons, onions, cucumbers, grapes.

-Note half-life 3-4hrs
- Oral BioAv low (40-50%)
Pathways:
- induce ROS production in cancer cells, but also known to reduce it.
Also a claim Fisetin-Induced Reactive Oxygen Species Production Has No Effect on Apoptosis in RCC cells
Also one claim (NAC 10-20mM levels) that NAC enhances ROS/apoptosis
- ROS↑ related: MMP↓(ΔΨm), ER Stress↑, UPR↑, GRP78↑, Ca+2↑, Cyt‑c↑, Caspases↑, DNA damage↑, cl-PARP↑, HSP↓
- Does not appear to lower antioxidants in cancer cells
- Raises AntiOxidant defense in Normal Cells: ROS↓, NRF2↑, SOD↑, GSH↑, Catalase↑,
- lowers Inflammation : NF-kB↓">NF-kB↓, COX2↓, p38↓, Pro-Inflammatory Cytokines : IL-1β↓, TNF-α↓, IL-6↓,
- inhibit Growth/Metastases : TumMeta↓, TumCG↓, EMT↓, MMPs↓, MMP2↓, MMP9↓, IGF-1↓, uPA↓, VEGF↓, FAK↓, RhoA↓, NF-κB↓, TGF-β↓, ERK↓
- cause Cell cycle arrest : TumCCA↑, cyclin D1↓, cyclin E↓, CDK2↓, CDK4↓, CDK6↓,
- inhibits Migration/Invasion : TumCMig↓, TumCI↓, FAK↓, ERK↓, EMT↓, TOP1↓, TET1↓,
- inhibits HIF-1α↓, cMyc↓, LDH↓, GRP78↑,
- inhibits angiogenesis↓ : VEGF↓, HIF-1α↓, EGFR↓,
- inhibits Cancer Stem Cells : CD133↓, β-catenin↓,
- Others: PI3K↓, AKT↓, JAK↓, STAT↓, Wnt↓, β-catenin↓, AMPK↓, ERK↓, JNK,
- Synergies: chemo-sensitization, chemoProtective, RadioSensitizer, Others(review target notes), Neuroprotective, Cognitive, Renoprotection, Hepatoprotective, CardioProtective,

- Selectivity: Cancer Cells vs Normal Cells

Fisetin effect on Cancer Cells

Rank	Pathway / Axis	Cancer Cells	Normal Cells	Label	Primary Interpretation	Notes
1	PI3K → AKT → mTOR axis	↓ AKT / ↓ mTOR signaling	↔ adaptive suppression	Driver	Loss of survival and growth signaling	Fisetin consistently suppresses pro-survival PI3K/AKT signaling, supporting growth inhibition and sensitization to stress
2	NF-κB signaling	↓ NF-κB activation	↓ inflammatory NF-κB tone	Driver	Suppression of inflammatory survival transcription	NF-κB inhibition contributes to anti-inflammatory effects and reduced tumor-supportive signaling
3	Reactive oxygen species (ROS)	↑ ROS (context- & dose-dependent)	↓ ROS	Conditional Driver	Biphasic redox modulation	Fisetin can act as a pro-oxidant in cancer cells at higher stress/dose while remaining antioxidant in normal cells
4	Mitochondrial integrity / intrinsic apoptosis	↓ ΔΨm; ↑ caspase activation	↔ preserved	Secondary	Execution of intrinsic apoptosis	Mitochondrial apoptosis occurs downstream of signaling and redox disruption
5	Cell cycle regulation	↑ G1 or G2/M arrest	↔ spared	Phenotypic	Cytostatic growth control	Cell-cycle arrest reflects upstream pathway inhibition rather than direct CDK blockade
6	Senescence / senolytic action	↑ senescence clearance (senescent-like tumor/stroma subsets)	↓ senescent cell burden (selective)	Secondary	Selective vulnerability of senescent-like cells	Fisetin is commonly described as senolytic; in cancer context this may impact tumor microenvironment and therapy-induced senescence
7	MAPK stress signaling (JNK / p38)	↑ JNK / ↑ p38 (context-dependent)	↔ minimal	Secondary	Stress-mediated apoptosis signaling	MAPK activation often follows ROS increase and supports apoptotic signaling
8	NRF2 antioxidant response	↑ NRF2 (adaptive, context-dependent)	↑ NRF2 (protective)	Adaptive	Stress compensation	NRF2 activation reflects redox buffering responses rather than primary cytotoxicity
9	Migration / invasion (EMT, MMP axis)	↓ migration & invasion	↔	Phenotypic	Anti-metastatic phenotype	Reduced EMT and protease activity limit invasive behavior downstream of signaling changes

NF-kB, Nuclear factor kappa B: Click to Expand ⟱

Source: HalifaxProj(inhibit)

Type:

NF-kB signaling
Nuclear factor kappa B (NF-κB) is a transcription factor that plays a crucial role in regulating immune response, inflammation, cell proliferation, and survival.
NF-κB is often found to be constitutively active in many types of cancer cells. This persistent activation can promote tumorigenesis by enhancing cell survival, proliferation, and metastasis.

Scientific Papers found: Click to Expand⟱

2857-

FIS,

A review on the chemotherapeutic potential of fisetin: In vitro evidences

Review,

Var,

COX2↓, PGE2↓, EGFR↓, Wnt↓, β-catenin/ZEB1↓, TCF↑, Apoptosis↑, Casp3↑, cl‑PARP↑, Bcl-2↓, Mcl-1↓, BAX↑, BIM↑, BAD↑, Akt↓, mTOR↓, ACC↑, Cyt‑c↑, Diablo↑, cl‑Casp8↑, Fas↑, DR5↑, TRAIL↑, Securin↓, CDC2↓, CDC25↓, HSP70/HSPA5↓, CDK2↓, CDK4↓, cycD1/CCND1↓, MMP2↓, uPA↓, NF-kB↓, cFos↓, cJun↓, MEK↓, p‑ERK↓, N-cadherin↓, Vim↓, Snail↓, Fibronectin↓, E-cadherin↓, NF-kB↑, ROS↑, DNAdam↑, MMP↓, CHOP↑, eff↑, ChemoSen↑,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:

Clinical Biomarkers ⓘ

EGFR↓, 1,
Total Targets: 50

Pathway results for Effect on Normal Cells:

Total Targets: 0

Scientific Paper Hit Count for: NF-kB, Nuclear factor kappa B

Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:78  Target#:214  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

Fisetin / NF-kB Cancer Research Results

Pathway results for Effect on Cancer / Diseased Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

Transcription & Epigenetics ⓘ

Protein Folding & ER Stress ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Immune & Inflammatory Signaling ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Pathway results for Effect on Normal Cells:

Home Page