Fisetin / P53 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


P53, P53-Guardian of the Genome: Click to Expand ⟱
Source: TCGA
Type: Proapototic
TP53 is the most commonly mutated gene in human cancer. TP53 is a gene that encodes for the p53 tumor suppressor protein ; TP73 (Chr.1p36.33) and TP63 (Chr.3q28) genes that encode transcription factors p73 and p63, respectively, are TP53 homologous structures.
p53 is a crucial tumor suppressor protein that plays a significant role in regulating the cell cycle, maintaining genomic stability, and preventing tumor formation. It is often referred to as the "guardian of the genome" due to its role in protecting cells from DNA damage and stress.
TP53 gene, which encodes the p53 protein, is one of the most frequently mutated genes in human cancers.
Overexpression of MDM2, an inhibitor of p53, can lead to decreased p53 activity even in the presence of wild-type p53.
In some cancers, particularly those with mutant p53, there may be an overexpression of the p53 protein.
Cancers with overexpression: Breast, lung, colorectal, overian, head and neck, Esophageal, bladder, pancreatic, and liver.
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
TumCCA↑, cl‑PARP↑, Apoptosis↑, Casp↑, P53↑, DR5↑, CHOP↑, ROS↑, ER Stress↑, ATF4↑, XBP-1↑, eff∅,
2852- FIS,    A comprehensive view on the fisetin impact on colorectal cancer in animal models: Focusing on cellular and molecular mechanisms
- Review, CRC, NA
Risk↓, P53↑, MDM2↓, COX2↓, Wnt↓, NF-kB↓, CDK2↓, CDK4↓, p‑RB1↓, cycE/CCNE↓, P21↑, NRF2↓, ROS↑, Casp8↑, Fas↑, TRAIL↑, DR5↑, MMP↓, Cyt‑c↑, selectivity↑, P450↝, GSTs↝, RadioS↑, Inflam↓, β-catenin/ZEB1↓, EGFR↓, TumCCA↑, ChemoSen↑,
2845- FIS,    Fisetin: A bioactive phytochemical with potential for cancer prevention and pharmacotherapy
- Review, Var, NA
PI3K↓, Akt↓, mTOR↓, p38↓, *antiOx↑, *neuroP↑, Casp3↑, Bcl-2↓, Mcl-1↓, BAX↑, BIM↑, BAD↑, AMPK↑, ACC↑, DNAdam↑, MMP↓, eff↑, ROS↑, cl‑PARP↑, Cyt‑c↑, Diablo↑, P53↑, p65↓, Myc↓, HSP70/HSPA5↓, HSP27↓, COX2↓, Wnt↓, EGFR↓, NF-kB↓, TumCCA↑, CDK2↓, CDK4↓, cycD1/CCND1↓, cycA1/CCNA1↓, P21↑, MMP2↓, MMP9↓, TumMeta↓, MMP1↓, MMP3↓, MMP7↓, MET↓, N-cadherin↓, Vim↓, Snail↓, Fibronectin↓, E-cadherin↑, uPA↓, ChemoSen↑, EMT↓, Twist↓, Zeb1↓, cFos↓, cJun↓, EGF↓, angioG↓, VEGF↓, eNOS↓, *NRF2↑, HO-1↑, NRF2↓, GSTs↓, ATF4↓,
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↝,
2828- FIS,    Fisetin, a Potent Anticancer Flavonol Exhibiting Cytotoxic Activity against Neoplastic Malignant Cells and Cancerous Conditions: A Scoping, Comprehensive Review
- Review, Var, NA
*neuroP↑, *antiOx↑, *Inflam↓, RenoP↑, COX2↓, Wnt↓, EGFR↓, NF-kB↓, Casp3↑, Ca+2↑, Casp8↑, TumCCA↑, CDK1↓, PI3K↓, Akt↓, mTOR↓, MAPK↓, *P53↓, *P21↓, *p16↓, mTORC1↓, mTORC2↓, P53↑, P21↑, cycD1/CCND1↓, cycA1/CCNA1↓, CDK2↓, CDK4↓, BAX↑, Bcl-2↓, PCNA↓, HER2/EBBR2↓, Cyt‑c↑, MMP↓, cl‑Casp9↑, MMP2↓, MMP9↓, cl‑PARP↑, uPA↓, DR4↑, DR5↑, ROS↓, AIF↑, CDC25↓, Dose↑, CHOP↑, ROS↑, cMyc↓, cardioP↑,
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↓,
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↓,
2842- FIS,    Fisetin inhibits cellular proliferation and induces mitochondria-dependent apoptosis in human gastric cancer cells
- in-vitro, GC, AGS
TumCCA↑, CDK2↓, P53↑, selectivity↑, MMP↓, DNAdam↑, cl‑PARP↑, mt-ROS↑, eff↓, survivin↓,
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 11 of 11

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 11

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSTs↓, 2,   GSTs↝, 1,   HO-1↑, 3,   Keap1↓, 1,   NRF2↓, 2,   NRF2↑, 3,   ROS↓, 5,   ROS↑, 9,   mt-ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 2,   CDC2↓, 1,   CDC25↓, 2,   EGF↓, 1,   MMP↓, 7,   mtDam↑, 1,   XIAP↓, 1,  

Core Metabolism/Glycolysis ⓘ

ACC↑, 1,   AMPK↑, 3,   cMyc↓, 1,  

Cell Death ⓘ

Akt↓, 7,   Apoptosis↑, 2,   BAD↑, 1,   Bak↑, 1,   BAX↑, 3,   Bcl-2↓, 3,   Bcl-xL↓, 1,   BID↑, 1,   BIM↑, 2,   Casp↑, 3,   Casp3↑, 7,   Casp7↑, 1,   Casp8↑, 4,   Casp9↑, 5,   cl‑Casp9↑, 1,   Cyt‑c↑, 7,   Diablo↑, 3,   DR4↑, 1,   DR5↑, 4,   Fas↑, 1,   IAP1↓, 1,   IAP2↓, 1,   iNOS↓, 1,   JNK↑, 2,   MAPK↓, 3,   MAPK↑, 1,   Mcl-1↓, 4,   MDM2↓, 1,   Myc↓, 1,   p27↑, 2,   p38↓, 2,   p38↑, 1,   survivin↓, 3,   TRAIL↑, 1,   TRAILR↑, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 2,   p70S6↓, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 3,   other↝, 1,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 3,   ER Stress↑, 4,   GRP78/BiP↑, 2,   HSF1↓, 1,   HSP27↓, 2,   HSP27↝, 1,   HSP70/HSPA5↓, 2,   HSP70/HSPA5↝, 1,   IRE1↑, 2,   XBP-1↑, 1,  

DNA Damage & Repair ⓘ

DNAdam↑, 5,   P53?, 1,   P53↑, 10,   cl‑PARP↑, 8,   PCNA↓, 1,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK2↓, 8,   CDK4↓, 7,   cycA1/CCNA1↓, 2,   cycD1/CCND1↓, 5,   cycE/CCNE↓, 4,   P21↑, 6,   p‑RB1↓, 1,   TumCCA↑, 9,  

Proliferation, Differentiation & Cell State ⓘ

CD133↓, 1,   CD44↓, 1,   cFos↓, 3,   CSCs↓, 1,   EMT↓, 5,   ERK↓, 3,   IGF-1↓, 1,   mTOR↓, 7,   mTORC1↓, 2,   mTORC2↓, 1,   PI3K↓, 6,   PTEN↑, 2,   TCF-4↓, 1,   TOP1↓, 1,   TOP2↓, 1,   TumCG↓, 3,   Wnt↓, 7,  

Migration ⓘ

AP-1↓, 1,   Ca+2↑, 2,   E-cadherin↑, 3,   FAK↓, 1,   Fibronectin↓, 1,   MET↓, 1,   MMP1↓, 2,   MMP2↓, 7,   MMP3↓, 2,   MMP7↓, 3,   MMP9↓, 7,   N-cadherin↓, 2,   PKCδ↓, 2,   Snail↓, 1,   TET1↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   TumCP↓, 2,   TumMeta↓, 2,   Twist↓, 2,   uPA↓, 6,   Vim↓, 3,   Zeb1↓, 1,   β-catenin/ZEB1↓, 3,  

Angiogenesis & Vasculature ⓘ

angioG↓, 3,   ATF4↓, 1,   ATF4↑, 3,   EGFR↓, 6,   eNOS↓, 1,   NO↓, 1,   NO↑, 1,   VEGF↓, 4,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 8,   IL6↓, 1,   Inflam↓, 2,   NF-kB↓, 9,   p65↓, 1,   PGE2↓, 5,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 4,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 2,   BioAv↑, 2,   ChemoSen↑, 5,   Dose↑, 1,   eff↓, 1,   eff↑, 4,   eff∅, 1,   Half-Life↝, 1,   P450↓, 1,   P450↝, 1,   RadioS↑, 3,   selectivity↑, 2,  

Clinical Biomarkers ⓘ

EGFR↓, 6,   HER2/EBBR2↓, 2,   IL6↓, 1,   Myc↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   RenoP↑, 1,   Risk↓, 1,  
Total Targets: 159

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   antiOx↑, 2,   GSH↑, 1,   HO-1↑, 1,   NRF2↑, 2,   ROS↓, 1,  

Core Metabolism/Glycolysis ⓘ

p‑cMyc↑, 1,  

DNA Damage & Repair ⓘ

p16↓, 1,   P53↓, 1,  

Cell Cycle & Senescence ⓘ

P21↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 2,  

Functional Outcomes ⓘ

neuroP↑, 2,  
Total Targets: 13

Scientific Paper Hit Count for: P53, P53-Guardian of the Genome
11 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#:236  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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