Fisetin / TumCMig 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


TumCMig, Tumor cell migration: Click to Expand ⟱
Source:
Type:
Tumor cell migration is a critical process in cancer progression and metastasis, which is the spread of cancer cells from the primary tumor to distant sites in the body.


Scientific Papers found: Click to Expand⟱
2847- FIS,    Fisetin-induced cell death, apoptosis, and antimigratory effects in cholangiocarcinoma cells
- in-vitro, CCA, NA
tumCV↓, ChemoSen↑, TumCMig↓, ROS↑, TumCI↓, angioG↓, CDK2↓, PI3K↓, Akt↓, mTOR↓, EGFR↓, Casp↑, mTORC1↓, mTORC2↑, cycD1/CCND1↓, cycE/CCNE↓, MMP2↓, MMP9↓, ER Stress↑, Ca+2↑, eff↓,
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
TumCI↓, TumCMig↓, EMT↓, E-cadherin↑, ZO-1↑, Vim↓, N-cadherin↓, MMP2↓, CD44↓, CD133↓, β-catenin/ZEB1↓, NF-kB↓, EGFR↓, STAT3↓, CSCs↓,
2824- FIS,    Fisetin in Cancer: Attributes, Developmental Aspects, and Nanotherapeutics
- Review, Var, NA
*antiOx↑, *Inflam↓, angioG↓, BioAv↓, BioAv↑, TumCP↓, TumCI↓, TumCMig↓, *neuroP↑, EMT↓, ROS↑, selectivity↑, EGFR↓, NF-kB↓, VEGF↓, MMP9↓, MMP↓, cl‑PARP↑, Casp7↑, Casp8↑, Casp9↑, *ROS↓, uPA↓, MMP1↓, Wnt↓, Akt↓, PI3K↓, ERK↓, Half-Life↝,
2830- FIS,    Biological effects and mechanisms of fisetin in cancer: a promising anti-cancer agent
- Review, Var, NA
TumCG↓, angioG↓, *ROS↓, TumCMig↓, VEGF↓, MAPK↑, NF-kB↓, PI3K↓, Akt↓, mTOR↓, NRF2↑, HO-1↑, ROS↓, Inflam↓, ER Stress↑, ROS↑, TumCP↓, ChemoSen↑, PTEN↑, P53↑, Casp3↑, Casp8↑, Casp9↑, COX2↓, Wnt↓, EGFR↓, Mcl-1↓, survivin↓, IAP1↓, IAP2↓, PGE2↓, β-catenin/ZEB1↓, DR5↑, MMP2↓, MMP9↓, FAK↓, uPA↓, EMT↓, ERK↓, JNK↑, p38↑, PKCδ↓, BioAv↓, BioAv↑, BioAv↑,
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↑,
2840- FIS,    Fisetin-induced cell death, apoptosis, and antimigratory effects in cholangiocarcinoma cells
- NA, CCA, NA
ROS↑, TumCMig↓, TumCP↓,

Showing Research Papers: 1 to 6 of 6

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 6

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress

HO-1↑, 1,   lipid-P↓, 1,   NRF2↑, 1,   ROS↓, 2,   ROS↑, 5,  

Mitochondria & Bioenergetics

EGF↓, 1,   MMP↓, 1,  

Cell Death

Akt↓, 4,   Apoptosis↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   Casp↑, 1,   Casp3↑, 1,   cl‑Casp3↑, 1,   Casp7↑, 1,   Casp8↑, 2,   Casp9↑, 2,   cl‑Casp9↑, 1,   Cyt‑c↑, 1,   DR5↑, 1,   IAP1↓, 1,   IAP2↓, 1,   JNK↑, 1,   MAPK↑, 1,   Mcl-1↓, 1,   p38↑, 1,   survivin↓, 1,  

Kinase & Signal Transduction

TSC2↑, 1,  

Transcription & Epigenetics

cJun↓, 1,   tumCV↓, 1,  

Protein Folding & ER Stress

ER Stress↑, 3,   GRP78/BiP↑, 1,   IRE1↑, 1,  

DNA Damage & Repair

DNAdam↑, 1,   P53↑, 1,   cl‑PARP↑, 1,  

Cell Cycle & Senescence

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

Proliferation, Differentiation & Cell State

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

Migration

AP-1↓, 1,   Ca+2↑, 1,   E-cadherin↑, 1,   FAK↓, 1,   MMP1↓, 1,   MMP2↓, 3,   MMP7↓, 1,   MMP9↓, 4,   N-cadherin↓, 1,   PKCδ↓, 1,   TGF-β↓, 1,   TumCA↓, 1,   TumCI↓, 4,   TumCMig↓, 6,   TumCP↓, 3,   uPA↓, 3,   Vim↓, 1,   ZO-1↑, 1,   β-catenin/ZEB1↓, 3,  

Angiogenesis & Vasculature

angioG↓, 3,   ATF4↑, 1,   EGFR↓, 5,   VEGF↓, 2,  

Barriers & Transport

P-gp↓, 1,  

Immune & Inflammatory Signaling

COX2↓, 2,   Inflam↓, 1,   NF-kB↓, 4,   PGE2↓, 1,  

Hormonal & Nuclear Receptors

AR↓, 1,  

Drug Metabolism & Resistance

BioAv↓, 2,   BioAv↑, 3,   ChemoSen↑, 3,   eff↓, 1,   eff↑, 2,   Half-Life↝, 1,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers

AR↓, 1,   EGFR↓, 5,  
Total Targets: 97

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress

antiOx↑, 1,   ROS↓, 2,  

Immune & Inflammatory Signaling

Inflam↓, 1,  

Functional Outcomes

neuroP↑, 1,  
Total Targets: 4

Scientific Paper Hit Count for: TumCMig, Tumor cell migration
6 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#:326  State#:%  Dir#:1
wNotes=0 sortOrder:rid,rpid

 

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