Fisetin / PGE2 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


PGE2, Prostaglandin E2: Click to Expand ⟱
Source:
Type:
Prostaglandin E2 (PGE2) is a lipid compound that plays a significant role in various physiological processes, including inflammation, immune response, and regulation of cell growth. PGE2 is often found at elevated levels in various types of cancer, including colorectal, breast, and lung cancers. It can promote tumor growth by enhancing cell proliferation, inhibiting apoptosis (programmed cell death), and promoting angiogenesis (the formation of new blood vessels).
- PGE2 is a pain-inducing factor. It is able to sensitize primary sensory neurons and leads to central sensitization and also facilitate the release of pain-related neuropeptides
-Upregulated in AD brain; promotes inflammatory cytokine release, increase ROS, may increase Aβ deposition
Scientific Papers found: Click to Expand⟱
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↑,
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 - NA, Colon, Caco-2
TumCG↓, other↝, Casp3↑, Casp7↑, PGE2↓, GSTs↓, Wnt↓, EGFR↓, NF-kB↓, COX2↓, P53↑, P21↑, P450↓,
2825- FIS,    Exploring the molecular targets of dietary flavonoid fisetin in cancer
- Review, Var, NA
*Inflam↓, *antiOx↓, *ERK↑, *p‑cMyc↑, *NRF2↑, *GSH↑, *HO-1↑, mTOR↓, PI3K↓, Akt↓, TumCCA↑, cycD1/CCND1↓, cycE/CCNE↓, CDK2↓, CDK4↓, CDK6↓, P21↑, p27↑, JNK↑, MMP2↓, MMP9↓, uPA↓, NF-kB↓, cFos↓, cJun↓, E-cadherin↑, Vim↓, N-cadherin↓, EMT↓, MMP↓, Cyt‑c↑, Diablo↑, Casp↑, cl‑PARP↑, P53↑, COX2↓, PGE2↓, HSP70/HSPA5↓, HSP27↓, DNAdam↑, Casp3↑, Casp9↑, ROS↑, AMPK↑, NO↑, Ca+2↑, mTORC1↓, p70S6↓, ROS↓, ER Stress↑, IRE1↑, ATF4↑, GRP78/BiP↑, eff↑, eff↑, eff↑, RadioS↑, ChemoSen↑, 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↑,
2832- FIS,    Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies
- Review, Var, NA
MMP↓, mtDam↑, Cyt‑c↑, Diablo↑, Casp↑, cl‑PARP↑, Bak↑, BIM↑, Bcl-xL↓, Bcl-2↓, P53↑, ROS↑, AMPK↑, Casp9↑, Casp3↑, BID↑, AIF↑, Akt↓, mTOR↓, MAPK↓, Wnt↓, β-catenin/ZEB1↓, TumCCA↑, P21↑, p27↑, cycD1/CCND1↓, cycE/CCNE↓, CDK2↓, CDK4↓, CDK6↓, TumMeta↓, uPA↓, E-cadherin↑, Vim↓, EMT↓, Twist↓, DNAdam↑, ROS↓, COX2↓, PGE2↓, HSF1↓, cFos↓, cJun↓, AP-1↓, Mcl-1↓, NF-kB↓, IRE1↑, ER Stress↑, ATF4↑, GRP78/BiP↑, MMP2↓, MMP9↓, TCF-4↓, MMP7↓, RadioS↑, TOP1↓, TOP2↓,
2843- FIS,    Fisetin and Quercetin: Promising Flavonoids with Chemopreventive Potential
- Review, Var, NA
NRF2↑, Keap1↓, ChemoSen↑, BioAv↓, Cyt‑c↑, Casp3↑, Casp9↑, BAX↑, tumCV↓, Mcl-1↓, cl‑PARP↑, IGF-1↓, Akt↓, CDK6↓, TumCCA↑, P53?, cycD1/CCND1↓, cycE/CCNE↓, CDK2↓, CDK4↓, CDK6↓, MMP2↓, MMP9↓, MMP1↓, MMP7↓, MMP3↓, VEGF↓, PI3K↓, mTOR↓, COX2↓, Wnt↓, EGFR↓, NF-kB↓, ERK↓, ROS↑, angioG↓, TNF-α↓, PGE2↓, iNOS↓, NO↓, IL6↓, HSP70/HSPA5↝, HSP27↝,

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 ⓘ

GSTs↓, 1,   HO-1↑, 1,   Keap1↓, 1,   NRF2↑, 2,   ROS↓, 3,   ROS↑, 5,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   CDC2↓, 1,   CDC25↓, 1,   MEK↓, 1,   MMP↓, 3,   mtDam↑, 1,  

Core Metabolism/Glycolysis ⓘ

ACC↑, 1,   AMPK↑, 2,  

Cell Death ⓘ

Akt↓, 5,   Apoptosis↑, 1,   BAD↑, 1,   Bak↑, 1,   BAX↑, 2,   Bcl-2↓, 2,   Bcl-xL↓, 1,   BID↑, 1,   BIM↑, 2,   Casp↑, 2,   Casp3↑, 6,   Casp7↑, 1,   Casp8↑, 1,   cl‑Casp8↑, 1,   Casp9↑, 4,   Cyt‑c↑, 4,   Diablo↑, 3,   DR5↑, 2,   Fas↑, 1,   IAP1↓, 1,   IAP2↓, 1,   iNOS↓, 1,   JNK↑, 2,   MAPK↓, 1,   MAPK↑, 1,   Mcl-1↓, 4,   p27↑, 2,   p38↑, 1,   survivin↓, 1,   TRAIL↑, 1,  

Kinase & Signal Transduction ⓘ

p70S6↓, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 3,   other↝, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 3,   GRP78/BiP↑, 2,   HSF1↓, 1,   HSP27↓, 1,   HSP27↝, 1,   HSP70/HSPA5↓, 2,   HSP70/HSPA5↝, 1,   IRE1↑, 2,  

DNA Damage & Repair ⓘ

DNAdam↑, 3,   P53?, 1,   P53↑, 4,   cl‑PARP↑, 4,  

Cell Cycle & Senescence ⓘ

CDK2↓, 4,   CDK4↓, 4,   cycD1/CCND1↓, 4,   cycE/CCNE↓, 3,   P21↑, 3,   Securin↓, 1,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

cFos↓, 3,   EMT↓, 3,   ERK↓, 2,   p‑ERK↓, 1,   IGF-1↓, 1,   mTOR↓, 5,   mTORC1↓, 1,   PI3K↓, 3,   PTEN↑, 1,   TCF↑, 1,   TCF-4↓, 1,   TOP1↓, 1,   TOP2↓, 1,   TumCG↓, 2,   Wnt↓, 5,  

Migration ⓘ

AP-1↓, 1,   Ca+2↑, 1,   E-cadherin↓, 1,   E-cadherin↑, 2,   FAK↓, 1,   Fibronectin↓, 1,   MMP1↓, 1,   MMP2↓, 5,   MMP3↓, 1,   MMP7↓, 2,   MMP9↓, 4,   N-cadherin↓, 2,   PKCδ↓, 1,   Snail↓, 1,   TumCMig↓, 1,   TumCP↓, 1,   TumMeta↓, 1,   Twist↓, 1,   uPA↓, 4,   Vim↓, 3,   β-catenin/ZEB1↓, 3,  

Angiogenesis & Vasculature ⓘ

angioG↓, 2,   ATF4↑, 2,   EGFR↓, 4,   NO↓, 1,   NO↑, 1,   VEGF↓, 2,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 6,   IL6↓, 1,   Inflam↓, 1,   NF-kB↓, 6,   NF-kB↑, 1,   PGE2↓, 6,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 4,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 2,   ChemoSen↑, 4,   eff↑, 4,   Half-Life↝, 1,   P450↓, 1,   RadioS↑, 2,  

Clinical Biomarkers ⓘ

EGFR↓, 4,   IL6↓, 1,  
Total Targets: 127

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   GSH↑, 1,   HO-1↑, 1,   NRF2↑, 1,   ROS↓, 1,  

Core Metabolism/Glycolysis ⓘ

p‑cMyc↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  
Total Targets: 8

Scientific Paper Hit Count for: PGE2, Prostaglandin E2
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#:248  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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