Fisetin / MDM2 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


MDM2, Double Minute 2 homolog: Click to Expand ⟱
Source:
Type: oncoprotein
Oncoprotein MDM2, a major ubiquitin E3 ligase of tumor suppressor p53; overexpression of MDM2 in human cancers is associated with a poor prognosis.
- A gene that encodes a protein involved in the regulation of the p53 tumor suppressor. The p53 protein plays a crucial role in controlling cell cycle progression, DNA repair, and apoptosis (programmed cell death). MDM2 functions primarily as an E3 ubiquitin ligase, which means it tags p53 for degradation, thereby regulating its levels in the cell.
-MDM2 is often overexpressed in various tumors, leading to the inhibition of p53 activity. This can result in uncontrolled cell proliferation, evasion of apoptosis, and increased genomic instability, all of which contribute to tumorigenesis.
Scientific Papers found: Click to Expand⟱
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↑,

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 ⓘ

GSTs↝, 1,   NRF2↓, 1,   ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

MMP↓, 1,  

Cell Death ⓘ

Casp8↑, 1,   Cyt‑c↑, 1,   DR5↑, 1,   Fas↑, 1,   MDM2↓, 1,   TRAIL↑, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,  

Cell Cycle & Senescence ⓘ

CDK2↓, 1,   CDK4↓, 1,   cycE/CCNE↓, 1,   P21↑, 1,   p‑RB1↓, 1,   TumCCA↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

Wnt↓, 1,  

Migration ⓘ

β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   Inflam↓, 1,   NF-kB↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   P450↝, 1,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,  

Functional Outcomes ⓘ

Risk↓, 1,  
Total Targets: 29

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: MDM2, Double Minute 2 homolog
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#:183  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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