Fisetin 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↓, 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

Scientific Papers found: Click to Expand⟱

2855-

FIS,

Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in Human Renal Carcinoma Caki Cells

in-vitro,

RCC,

Caki-1

"highlight2" >TumCCA↑, "highlight2" >cl‑PARP↑, "highlight2" >Apoptosis↑, "highlight2" >Casp↑, "highlight2" >P53↑, "highlight2" >DR5↑, "highlight2" >CHOP↑, "highlight2" >ROS↑, "highlight2" >ER Stress↑, "highlight2" >ATF4↑, "highlight2" >XBP-1↑, "highlight2" >eff∅,

2846-

FIS,

Fisetin protects against cardiac cell death through reduction of ROS production and caspases activity

in-vitro,

Nor,

0, 5, 10, 15, 20, 30, 40, 60, 80 and 100 μM

concentration of 15 μM of fisetin in the subsequent experiments

"highlight2" >*cardioP↑, "highlight2" >*ROS↓, "highlight2" >*Casp↓, "highlight2" >*DNAdam↓,

2847-

FIS,

Fisetin-induced cell death, apoptosis, and antimigratory effects in cholangiocarcinoma cells

in-vitro,

CCA,

"highlight2" >tumCV↓, "highlight2" >ChemoSen↑, "highlight2" >TumCMig↓, "highlight2" >ROS↑, "highlight2" >TumCI↓, "highlight2" >angioG↓, "highlight2" >CDK2↓, "highlight2" >PI3K↓, "highlight2" >Akt↓, "highlight2" >mTOR↓, "highlight2" >EGFR↓, "highlight2" >Casp↑, "highlight2" >mTORC1↓, "highlight2" >mTORC2↑, "highlight2" >cycD1/CCND1↓, "highlight2" >cycE/CCNE↓, "highlight2" >MMP2↓, "highlight2" >MMP9↓, "highlight2" >ER Stress↑, "highlight2" >Ca+2↑, "highlight2" >eff↓,

2848-

FIS,

Fisetin alleviates cellular senescence through PTEN mediated inhibition of PKCδ-NOX1 pathway in vascular smooth muscle cells

in-vitro,

Nor,

"highlight2" >*ROS↓, "highlight2" >*PTEN↑, "highlight2" >*PKCδ↑, "highlight2" >*Inflam↓,

2849-

FIS,

Activation of reactive oxygen species/AMP activated protein kinase signaling mediates fisetin-induced apoptosis in multiple myeloma U266 cells

in-vitro,

Melanoma,

U266

40 μg/ml

"highlight2" >TumCD↑, "highlight2" >TumCCA↑, "highlight2" >Casp3↑, "highlight2" >Bcl-2↓, "highlight2" >Mcl-1↓, "highlight2" >BAX↑, "highlight2" >BIM↑, "highlight2" >BAD↑, "highlight2" >AMPK↑, "highlight2" >ACC↑, "highlight2" >p‑Akt↓, "highlight2" >p‑mTOR↓, "highlight2" >ROS↑, "highlight2" >eff↓,

2850-

FIS,

Fisetin regulates TPA-induced breast Cancer cell invasion by suppressing matrix metalloproteinase-9 activation via the PKC/ROS/MAPK pathways

in-vitro,

BC,

MCF-7

"highlight2" >TumCI↓, "highlight2" >PKCδ↓, "highlight2" >ROS↓, "highlight2" >ERK↑, "highlight2" >p38↓, "highlight2" >NF-kB↓, "highlight2" >MMP9↓,

2851-

FIS,

Apoptosis induction in breast cancer cell lines by the dietary flavonoid fisetin

in-vitro,

BC,

MDA-MB-468

in-vitro,

BC,

MDA-MB-231

in-vitro,

BC,

MCF-7

in-vitro,

BC,

T47D

in-vitro,

BC,

SkBr3

in-vitro,

Nor,

"highlight2" >tumCV↓, "highlight2" >selectivity↑, "highlight2" >TumCCA↑, "highlight2" >Apoptosis↑, "highlight2" >ROS∅,

2852-

FIS,

A comprehensive view on the fisetin impact on colorectal cancer in animal models: Focusing on cellular and molecular mechanisms

Review,

CRC,

"highlight2" >Risk↓, "highlight2" >P53↑, "highlight2" >MDM2↓, "highlight2" >COX2↓, "highlight2" >Wnt↓, "highlight2" >NF-kB↓, "highlight2" >CDK2↓, "highlight2" >CDK4↓, "highlight2" >p‑RB1↓, "highlight2" >cycE/CCNE↓, "highlight2" >P21↑, "highlight2" >NRF2↓, "highlight2" >ROS↑, "highlight2" >Casp8↑, "highlight2" >Fas↑, "highlight2" >TRAIL↑, "highlight2" >DR5↑, "highlight2" >MMP↓, "highlight2" >Cyt‑c↑, "highlight2" >selectivity↑, "highlight2" >P450↝, "highlight2" >GSTs↝, "highlight2" >RadioS↑, "highlight2" >Inflam↓, "highlight2" >β-catenin/ZEB1↓, "highlight2" >EGFR↓, "highlight2" >TumCCA↑, "highlight2" >ChemoSen↑,

2853-

FIS,

Fisetin Inhibits Cell Proliferation and Induces Apoptosis via JAK/STAT3 Signaling Pathways in Human Thyroid TPC 1 Cancer Cells

in-vitro,

Thyroid,

TPC-1

"highlight2" >Apoptosis↑, "highlight2" >ROS↑, "highlight2" >MMP↓, "highlight2" >TumCCA↑, "highlight2" >Casp3↑, "highlight2" >Casp8↑, "highlight2" >Casp9↑, "highlight2" >JAK1↓, "highlight2" >STAT3↓,

2854-

FIS,

New Perspectives for Fisetin

Review,

Var,

Review,

Stroke,

"highlight2" >Inflam↓, "highlight2" >ChemoSen↑, "highlight2" >chemoPv↑, "highlight2" >eff↑, "highlight2" >memory↑, "highlight2" >neuroP↑, "highlight2" >*Dose↑, "highlight2" >BioAv↓, "highlight2" >BBB↑,

2845-

FIS,

Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy

Review,

Var,

"highlight2" >PI3K↓, "highlight2" >Akt↓, "highlight2" >mTOR↓, "highlight2" >p38↓, "highlight2" >*antiOx↑, "highlight2" >*neuroP↑, "highlight2" >Casp3↑, "highlight2" >Bcl-2↓, "highlight2" >Mcl-1↓, "highlight2" >BAX↑, "highlight2" >BIM↑, "highlight2" >BAD↑, "highlight2" >AMPK↑, "highlight2" >ACC↑, "highlight2" >DNAdam↑, "highlight2" >MMP↓, "highlight2" >eff↑, "highlight2" >ROS↑, "highlight2" >cl‑PARP↑, "highlight2" >Cyt‑c↑, "highlight2" >Diablo↑, "highlight2" >P53↑, "highlight2" >p65↓, "highlight2" >Myc↓, "highlight2" >HSP70/HSPA5↓, "highlight2" >HSP27↓, "highlight2" >COX2↓, "highlight2" >Wnt↓, "highlight2" >EGFR↓, "highlight2" >NF-kB↓, "highlight2" >TumCCA↑, "highlight2" >CDK2↓, "highlight2" >CDK4↓, "highlight2" >cycD1/CCND1↓, "highlight2" >cycA1/CCNA1↓, "highlight2" >P21↑, "highlight2" >MMP2↓, "highlight2" >MMP9↓, "highlight2" >TumMeta↓, "highlight2" >MMP1↓, "highlight2" >MMP3↓, "highlight2" >MMP7↓, "highlight2" >MET↓, "highlight2" >N-cadherin↓, "highlight2" >Vim↓, "highlight2" >Snail↓, "highlight2" >Fibronectin↓, "highlight2" >E-cadherin↑, "highlight2" >uPA↓, "highlight2" >ChemoSen↑, "highlight2" >EMT↓, "highlight2" >Twist↓, "highlight2" >Zeb1↓, "highlight2" >cFos↓, "highlight2" >cJun↓, "highlight2" >EGF↓, "highlight2" >angioG↓, "highlight2" >VEGF↓, "highlight2" >eNOS↓, "highlight2" >*NRF2↑, "highlight2" >HO-1↑, "highlight2" >NRF2↓, "highlight2" >GSTs↓, "highlight2" >ATF4↓,

2856-

FIS,

N -acetyl- L -cysteine enhances fisetin-induced cytotoxicity via induction of ROS-independent apoptosis in human colonic cancer cells

in-vitro,

Colon,

COLO205

"highlight2" >eff↑, "highlight2" >ROS↑, "highlight2" >tumCV↓, "highlight2" >Casp3↑, "highlight2" >Bcl-2↓, "highlight2" >MMP↓, "highlight2" >eff↑,

2857-

FIS,

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

Review,

Var,

"highlight2" >COX2↓, "highlight2" >PGE2↓, "highlight2" >EGFR↓, "highlight2" >Wnt↓, "highlight2" >β-catenin/ZEB1↓, "highlight2" >TCF↑, "highlight2" >Apoptosis↑, "highlight2" >Casp3↑, "highlight2" >cl‑PARP↑, "highlight2" >Bcl-2↓, "highlight2" >Mcl-1↓, "highlight2" >BAX↑, "highlight2" >BIM↑, "highlight2" >BAD↑, "highlight2" >Akt↓, "highlight2" >mTOR↓, "highlight2" >ACC↑, "highlight2" >Cyt‑c↑, "highlight2" >Diablo↑, "highlight2" >cl‑Casp8↑, "highlight2" >Fas↑, "highlight2" >DR5↑, "highlight2" >TRAIL↑, "highlight2" >Securin↓, "highlight2" >CDC2↓, "highlight2" >CDC25↓, "highlight2" >HSP70/HSPA5↓, "highlight2" >CDK2↓, "highlight2" >CDK4↓, "highlight2" >cycD1/CCND1↓, "highlight2" >MMP2↓, "highlight2" >uPA↓, "highlight2" >NF-kB↓, "highlight2" >cFos↓, "highlight2" >cJun↓, "highlight2" >MEK↓, "highlight2" >p‑ERK↓, "highlight2" >N-cadherin↓, "highlight2" >Vim↓, "highlight2" >Snail↓, "highlight2" >Fibronectin↓, "highlight2" >E-cadherin↓, "highlight2" >NF-kB↑, "highlight2" >ROS↑, "highlight2" >DNAdam↑, "highlight2" >MMP↓, "highlight2" >CHOP↑, "highlight2" >eff↑, "highlight2" >ChemoSen↑,

2858-

FIS,

Fisetin inhibits cell migration via inducing HO-1 and reducing MMPs expression in breast cancer cell lines

in-vitro,

BC,

4T1

"highlight2" >HO-1↑, "highlight2" >NRF2↑, "highlight2" >MMP2↓, "highlight2" >MMP9↓,

2859-

FIS,

The Natural Flavonoid Fisetin Inhibits Cellular Proliferation of Hepatic, Colorectal, and Pancreatic Cancer Cells through Modulation of Multiple Signaling Pathways

in-vitro,

Liver,

HepG2

3.2μM

NA,

Colon,

Caco-2

16.4 μM

"highlight2" >TumCG↓, "highlight2" >other↝, "highlight2" >Casp3↑, "highlight2" >Casp7↑, "highlight2" >PGE2↓, "highlight2" >GSTs↓, "highlight2" >Wnt↓, "highlight2" >EGFR↓, "highlight2" >NF-kB↓, "highlight2" >COX2↓, "highlight2" >P53↑, "highlight2" >P21↑, "highlight2" >P450↓,

2860-

FIS,

Fisetin induces autophagy in pancreatic cancer cells via endoplasmic reticulum stress- and mitochondrial stress-dependent pathways

in-vitro,

PC,

PANC1

in-vitro,

PC,

Bxpc-3

in-vitro,

Nor,

hTERT-HPNE

in-vivo,

NA,

mice

"highlight2" >AMPK↑, "highlight2" >mTOR↑, "highlight2" >UPR↑, "highlight2" >ER Stress↑, "highlight2" >selectivity↑, "highlight2" >TumCP↓, "highlight2" >PERK↑, "highlight2" >ATF4↑, "highlight2" >ATF6↑,

2861-

FIS,

The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress

Review,

Nor,

Review,

Stroke,

Review,

Park,

"highlight2" >*antiOx↑, "highlight2" >*ROS↓, "highlight2" >*neuroP↑, "highlight2" >*NO↑, "highlight2" >BioAv↝, "highlight2" >*BBB↑, "highlight2" >*toxicity↑, "highlight2" >*eff↑, "highlight2" >*GSH↑, "highlight2" >*SOD↑, "highlight2" >*Aβ↓, "highlight2" >*12LOX↓, "highlight2" >*COX2↓, "highlight2" >*Catalase↑, "highlight2" >*Inflam↓, "highlight2" >*TNF-α↓, "highlight2" >*IL6↑, "highlight2" >*lipid-P↓, "highlight2" >NF-kB↓, "highlight2" >IL1β↓, "highlight2" >NRF2↑, "highlight2" >HO-1↑, "highlight2" >GSTs↑, "highlight2" >cognitive↑, "highlight2" >*BDNF↑,

2862-

FIS,

Fisetin averts oxidative stress in pancreatic tissues of streptozotocin-induced diabetic rat

in-vivo,

Diabetic,

"highlight2" >*BG↓, "highlight2" >*NF-kB↓, "highlight2" >*IL1β↓, "highlight2" >*NO↓, "highlight2" >*Insulin↑, "highlight2" >*SOD↑, "highlight2" >*Catalase↑, "highlight2" >*GPx↑, "highlight2" >*GSTs↑,

5392-

FIS,

AsP,

Fisetin topical delivery via ascorbyl palmitate/hyaluronan-enhanced limosomes: a novel paradigm for preventing UVB-induced skin photoaging

in-vivo,

Nor,

"highlight2" >eff↑, "highlight2" >*antiOx↑, "highlight2" >*MMP9↓, "highlight2" >*TNF-α↓, "highlight2" >*NF-kB↓, "highlight2" >*SOD↑, "highlight2" >*Catalase↑, "highlight2" >*AntiAge↑, "highlight2" >*Inflam↓, "highlight2" >*JNK↓,

2831-

FIS,

Fisetin as a chemoprotective and chemotherapeutic agent: mechanistic insights and future directions in cancer therapy

Review,

Var,

"highlight2" >TumCG↓, "highlight2" >ER Stress↑, "highlight2" >antiOx↓, "highlight2" >ROS↓, "highlight2" >ChemoSen↑,

1113-

FIS,

Fisetin suppresses migration, invasion and stem-cell-like phenotype of human non-small cell lung carcinoma cells via attenuation of epithelial to mesenchymal transition

in-vitro,

Lung,

A549

in-vitro,

Lung,

H1299

"highlight2" >TumCI↓, "highlight2" >TumCMig↓, "highlight2" >EMT↓, "highlight2" >E-cadherin↑, "highlight2" >ZO-1↑, "highlight2" >Vim↓, "highlight2" >N-cadherin↓, "highlight2" >MMP2↓, "highlight2" >CD44↓, "highlight2" >CD133↓, "highlight2" >β-catenin/ZEB1↓, "highlight2" >NF-kB↓, "highlight2" >EGFR↓, "highlight2" >STAT3↓, "highlight2" >CSCs↓,

2824-

FIS,

Fisetin in Cancer: Attributes, Developmental Aspects, and Nanotherapeutics

Review,

Var,

"highlight2" >*antiOx↑, "highlight2" >*Inflam↓, "highlight2" >angioG↓, "highlight2" >BioAv↓, "highlight2" >BioAv↑, "highlight2" >TumCP↓, "highlight2" >TumCI↓, "highlight2" >TumCMig↓, "highlight2" >*neuroP↑, "highlight2" >EMT↓, "highlight2" >ROS↑, "highlight2" >selectivity↑, "highlight2" >EGFR↓, "highlight2" >NF-kB↓, "highlight2" >VEGF↓, "highlight2" >MMP9↓, "highlight2" >MMP↓, "highlight2" >cl‑PARP↑, "highlight2" >Casp7↑, "highlight2" >Casp8↑, "highlight2" >Casp9↑, "highlight2" >*ROS↓, "highlight2" >uPA↓, "highlight2" >MMP1↓, "highlight2" >Wnt↓, "highlight2" >Akt↓, "highlight2" >PI3K↓, "highlight2" >ERK↓, "highlight2" >Half-Life↝,

2825-

FIS,

Exploring the molecular targets of dietary flavonoid fisetin in cancer

Review,

Var,

"highlight2" >*Inflam↓, "highlight2" >*antiOx↓, "highlight2" >*ERK↑, "highlight2" >*p‑cMyc↑, "highlight2" >*NRF2↑, "highlight2" >*GSH↑, "highlight2" >*HO-1↑, "highlight2" >mTOR↓, "highlight2" >PI3K↓, "highlight2" >Akt↓, "highlight2" >TumCCA↑, "highlight2" >cycD1/CCND1↓, "highlight2" >cycE/CCNE↓, "highlight2" >CDK2↓, "highlight2" >CDK4↓, "highlight2" >CDK6↓, "highlight2" >P21↑, "highlight2" >p27↑, "highlight2" >JNK↑, "highlight2" >MMP2↓, "highlight2" >MMP9↓, "highlight2" >uPA↓, "highlight2" >NF-kB↓, "highlight2" >cFos↓, "highlight2" >cJun↓, "highlight2" >E-cadherin↑, "highlight2" >Vim↓, "highlight2" >N-cadherin↓, "highlight2" >EMT↓, "highlight2" >MMP↓, "highlight2" >Cyt‑c↑, "highlight2" >Diablo↑, "highlight2" >Casp↑, "highlight2" >cl‑PARP↑, "highlight2" >P53↑, "highlight2" >COX2↓, "highlight2" >PGE2↓, "highlight2" >HSP70/HSPA5↓, "highlight2" >HSP27↓, "highlight2" >DNAdam↑, "highlight2" >Casp3↑, "highlight2" >Casp9↑, "highlight2" >ROS↑, "highlight2" >AMPK↑, "highlight2" >NO↑, "highlight2" >Ca+2↑,

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 39

Pathway results for Effect on Normal Cells:

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#:%  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

Fisetin Cancer Research Results

Pathway results for Effect on Normal Cells:

Redox & Oxidative Stress ⓘ

Mitochondria & Bioenergetics ⓘ

Core Metabolism/Glycolysis ⓘ

Cell Death ⓘ

DNA Damage & Repair ⓘ

Cell Cycle & Senescence ⓘ

Proliferation, Differentiation & Cell State ⓘ

Migration ⓘ

Angiogenesis & Vasculature ⓘ

Barriers & Transport ⓘ

Immune & Inflammatory Signaling ⓘ

Synaptic & Neurotransmission ⓘ

Protein Aggregation ⓘ

Drug Metabolism & Resistance ⓘ

Clinical Biomarkers ⓘ

Functional Outcomes ⓘ

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