Fisetin / Endon 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


Endon, endonuclease: Click to Expand ⟱
Source:
Type:
Endonucleases are enzymes that play a crucial role in the maintenance of genome stability by cleaving the phosphodiester backbone of DNA. In the context of cancer, endonucleases can have both tumor-suppressing and tumor-promoting effects.

1. APEX1 (Apurinic/Apyrimidinic Endonuclease 1)
Cancers: Breast cancer, lung cancer, colorectal cancer Prognosis: High expression is often associated with poor prognosis due to its role in DNA repair and resistance to chemotherapy.
2. FEN1 (Flap Endonuclease 1)
Cancers: Breast cancer, prostate cancer, pancreatic cancer
Prognosis: Overexpression is linked to increased tumor aggressiveness and poor survival rates.
3. EXO1 (Exonuclease 1)
Cancers: Colorectal cancer, ovarian cancer
Prognosis: High levels of EXO1 expression can correlate with poor prognosis and increased risk of metastasis.
4. DNase I (Deoxyribonuclease I)
Cancers: Various solid tumors
Prognosis: Altered expression levels can be indicative of tumor progression and immune evasion. 5. Caspase-3 (an endonuclease involved in apoptosis)
Cancers: Various cancers, including leukemia and solid tumors
Prognosis: High levels of active caspase-3 are often associated with increased apoptosis and may correlate with better treatment responses.
6. Rad51 (a recombinase with endonuclease activity)
Cancers: Breast cancer, ovarian cancer
Prognosis: Elevated expression is often linked to resistance to DNA-damaging therapies and poor prognosis.
7. MRE11 (part of the MRN complex)
Cancers: Breast cancer, lung cancer
Prognosis: Altered expression can indicate defects in DNA repair mechanisms, influencing treatment outcomes.
8. TDP1 (Tyrosyl-DNA Phosphodiesterase 1)
Cancers: Glioblastoma, breast cancer
Prognosis: High expression levels may be associated with resistance to certain chemotherapeutic agents.
9. UNG (Uracil-DNA Glycosylase)
Cancers: Colorectal cancer, lung cancer
Prognosis: Its expression can influence the mutation rate and may correlate with tumor aggressiveness.
10. LIG3 (DNA Ligase III)
Cancers: Various cancers, including breast and prostate cancer
Prognosis: Overexpression may be linked to enhanced DNA repair capabilities, contributing to treatment resistance.
Scientific Papers found: Click to Expand⟱
3372- QC,  FIS,  KaempF,    Anticancer Potential of Selected Flavonols: Fisetin, Kaempferol, and Quercetin on Head and Neck Cancers
- Review, HNSCC, NA
ROCK1↑, TumCCA↓, HSPs↓, RAS↓, ROS↑, Ca+2↑, MMP↓, Cyt‑c↑, Endon↑, MMP9↓, MMP2↓, MMP7↓, MMP-10↓, VEGF↓, NF-kB↓, p65↓, iNOS↓, COX2↓, uPA↓, PI3K↓, FAK↓, MEK↓, ERK↓, JNK↓, p38↓, cJun↓, FOXO3↑,

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:


Redox & Oxidative Stress ⓘ

ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

MEK↓, 1,   MMP↓, 1,  

Cell Death ⓘ

Cyt‑c↑, 1,   Endon↑, 1,   iNOS↓, 1,   JNK↓, 1,   p38↓, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 1,  

Protein Folding & ER Stress ⓘ

HSPs↓, 1,  

Cell Cycle & Senescence ⓘ

TumCCA↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↓, 1,   FOXO3↑, 1,   PI3K↓, 1,   RAS↓, 1,  

Migration ⓘ

Ca+2↑, 1,   FAK↓, 1,   MMP-10↓, 1,   MMP2↓, 1,   MMP7↓, 1,   MMP9↓, 1,   ROCK1↑, 1,   uPA↓, 1,  

Angiogenesis & Vasculature ⓘ

VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   NF-kB↓, 1,   p65↓, 1,  
Total Targets: 27

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: Endon, endonuclease
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#:635  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

Home Page