Fisetin / Apoptosis 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


Apoptosis, Apoptosis: Click to Expand ⟱
Source:
Type: type of cell death
Situation in which a cell actively pursues a course toward death upon receiving certain stimuli.
Cancer is one of the scenarios where too little apoptosis occurs, resulting in malignant cells that will not die.
Scientific Papers found: Click to Expand⟱
2855- FIS,    Apoptosis_Through_p53-Mediated_Up-Regulation_of_DR5_Expression_in_Human_Renal_Carcinoma_Caki_Cells">Fisetin Induces Apoptosis Through p53-Mediated Up-Regulation of DR5 Expression in Human Renal Carcinoma Caki Cells
- in-vitro, RCC, Caki-1
TumCCA↑, cl‑PARP↑, Apoptosis↑, Casp↑, P53↑, DR5↑, CHOP↑, ROS↑, ER Stress↑, ATF4↑, XBP-1↑, eff∅,
2851- FIS,    Apoptosis-induction-in-breast-cancer">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, NA
tumCV↓, selectivity↑, TumCCA↑, Apoptosis↑, ROS∅,
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
Apoptosis↑, ROS↑, MMP↓, TumCCA↑, Casp3↑, Casp8↑, Casp9↑, JAK1↓, STAT3↓,
2857- FIS,    A review on the chemotherapeutic potential of fisetin: In vitro evidences
- Review, Var, NA
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↑,
2826- FIS,    Fisetin induces apoptosis in breast cancer MDA-MB-453 cells through degradation of HER2/neu and via the PI3K/Akt pathway
- in-vitro, BC, MDA-MB-453
Apoptosis↑, p‑ENO1↓, DNAdam↑, PI3K↑, p‑Akt↑, HER2/EBBR2↓,
2829- FIS,    Fisetin: An anticancer perspective
- Review, Var, NA
TumCP↓, TumCI↓, TumCCA↑, TumCG↓, Apoptosis↑, cl‑PARP↑, PKCδ↓, ROS↓, ERK↓, NF-kB↓, survivin↓, ROS↑, PI3K↓, Akt↓, mTOR↓, MAPK↓, p38↓, HER2/EBBR2↓, EMT↓, PTEN↑, HO-1↑, NRF2↑, MMP2↓, MMP9↓, MMP↓, Casp8↑, Casp9↑, TRAILR↑, Cyt‑c↑, XIAP↓, P53↑, CDK2↓, CDK4↓, CDC25↓, CDC2↓, VEGF↓, DNAdam↑, TET1↓, CHOP↑, CD44↓, CD133↓, uPA↓, CSCs↓,
2839- FIS,    Dietary flavonoid fisetin for cancer prevention and treatment
- Review, Var, NA
DNAdam↑, ROS↑, Apoptosis↑, Bcl-2↓, BAX↑, cl‑Casp9↑, cl‑Casp3↑, Cyt‑c↑, lipid-P↓, TumCG↓, TumCA↓, TumCMig↓, TumCI↓, uPA↓, ERK↓, MMP9↓, NF-kB↓, cFos↓, cJun↓, AP-1↓, TumCCA↑, AR↓, mTORC1↓, mTORC2↓, TSC2↑, EGF↓, TGF-β↓, EMT↓, P-gp↓, PI3K↓, Akt↓, mTOR↓, eff↑, ROS↓, ER Stress↑, IRE1↑, ATF4↑, GRP78/BiP↑, ChemoSen↑, CDK2↓, CDK4↓, cycE/CCNE↓, cycD1/CCND1↓, P21↑, COX2↓, Wnt↓, EGFR↓, β-catenin/ZEB1↓, TCF-4↓, MMP7↓, RadioS↑, eff↑,
2844- FIS,    Fisetin, a dietary flavonoid induces apoptosis via modulating the MAPK and PI3K/Akt signalling pathways in human osteosarcoma (U-2 OS) cells
- in-vitro, OS, U2OS
tumCV↓, Apoptosis↑, Casp3↑, Casp8↑, Casp9↑, BAX↑, BAD↑, Bcl-2↓, Bcl-xL↓, PI3K↓, Akt↓, ERK↓, p‑JNK↑, p‑cJun↑, p‑p38↑, ROS↑, MMP↓, mTORC1↓, PTEN↑, p‑GSK‐3β↓, GSK‐3β↑, NF-kB↓, IKKα↑, Cyt‑c↑,

Showing Research Papers: 1 to 8 of 8

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 8

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

HO-1↑, 1,   lipid-P↓, 1,   NRF2↑, 1,   ROS↓, 2,   ROS↑, 6,   ROS∅, 1,  

Mitochondria & Bioenergetics ⓘ

CDC2↓, 2,   CDC25↓, 2,   EGF↓, 1,   MEK↓, 1,   MMP↓, 4,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACC↑, 1,   p‑ENO1↓, 1,  

Cell Death ⓘ

Akt↓, 4,   p‑Akt↑, 1,   Apoptosis↑, 8,   BAD↑, 2,   BAX↑, 3,   Bcl-2↓, 3,   Bcl-xL↓, 1,   BIM↑, 1,   Casp↑, 1,   Casp3↑, 3,   cl‑Casp3↑, 1,   Casp8↑, 3,   cl‑Casp8↑, 1,   Casp9↑, 3,   cl‑Casp9↑, 1,   Cyt‑c↑, 4,   Diablo↑, 1,   DR5↑, 2,   Fas↑, 1,   p‑JNK↑, 1,   MAPK↓, 1,   Mcl-1↓, 1,   p38↓, 1,   p‑p38↑, 1,   survivin↓, 1,   TRAIL↑, 1,   TRAILR↑, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 2,   TSC2↑, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 2,   p‑cJun↑, 1,   tumCV↓, 2,  

Protein Folding & ER Stress ⓘ

CHOP↑, 3,   ER Stress↑, 2,   GRP78/BiP↑, 1,   HSP70/HSPA5↓, 1,   IRE1↑, 1,   XBP-1↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 4,   P53↑, 2,   cl‑PARP↑, 3,  

Cell Cycle & Senescence ⓘ

CDK2↓, 3,   CDK4↓, 3,   cycD1/CCND1↓, 2,   cycE/CCNE↓, 1,   P21↑, 1,   Securin↓, 1,   TumCCA↑, 5,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 1,   CD44↓, 1,   cFos↓, 2,   CSCs↓, 1,   EMT↓, 2,   ERK↓, 3,   p‑ERK↓, 1,   GSK‐3β↑, 1,   p‑GSK‐3β↓, 1,   mTOR↓, 3,   mTORC1↓, 2,   mTORC2↓, 1,   PI3K↓, 3,   PI3K↑, 1,   PTEN↑, 2,   STAT3↓, 1,   TCF↑, 1,   TCF-4↓, 1,   TumCG↓, 2,   Wnt↓, 2,  

Migration ⓘ

AP-1↓, 1,   E-cadherin↓, 1,   Fibronectin↓, 1,   MMP2↓, 2,   MMP7↓, 1,   MMP9↓, 2,   N-cadherin↓, 1,   PKCδ↓, 1,   Snail↓, 1,   TET1↓, 1,   TGF-β↓, 1,   TumCA↓, 1,   TumCI↓, 2,   TumCMig↓, 1,   TumCP↓, 1,   uPA↓, 3,   Vim↓, 1,   β-catenin/ZEB1↓, 2,  

Angiogenesis & Vasculature ⓘ

ATF4↑, 2,   EGFR↓, 2,   VEGF↓, 1,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   IKKα↑, 1,   JAK1↓, 1,   NF-kB↓, 4,   NF-kB↑, 1,   PGE2↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 2,   eff↑, 3,   eff∅, 1,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 2,   HER2/EBBR2↓, 2,  
Total Targets: 119

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Apoptosis, Apoptosis
8 Fisetin
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#:14  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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