Fisetin / ZO-1 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


ZO-1, Zonula occludens-1: Click to Expand ⟱
Source:
Type:
ZO-1 (Zonula occludens-1) is a protein that plays a crucial role in the formation and maintenance of tight junctions in epithelial cells. Tight junctions are essential for maintaining the integrity of epithelial barriers and regulating the passage of ions and molecules across the cell membrane.

In the context of cancer, ZO-1 has been implicated in several ways:

1.Loss of ZO-1 expression: Reduced or lost expression observed in various types of cancer.
2.Disruption of tight junctions: Cancer cells often exhibit disrupted tight junctions, which can lead to increased permeability and the loss of epithelial barrier function. ZO-1 is a key component of tight junctions, and its disruption can contribute to the development and progression of cancer.
3.Epithelial-to-mesenchymal transition (EMT): ZO-1 has been shown to play a role in regulating EMT, a process by which epithelial cells acquire a mesenchymal phenotype. EMT is a key event in the development of cancer metastasis, and ZO-1's role in regulating this process is an area of active research.
4.Tumor suppressor function: ZO-1 has been proposed to have tumor suppressor functions, and its loss or downregulation can contribute to the development of cancer. ZO-1's tumor suppressor functions may be related to its ability to regulate cell growth, apoptosis, and cell migration.

ZO-1 generally acts as a tumor suppressor by maintaining epithelial integrity. In many cancers, downregulation or mislocalization of ZO-1 is observed and is associated with a poorer prognosis due to the facilitation of EMT and metastasis.
Scientific Papers found: Click to Expand⟱
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↓,

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:


Proliferation, Differentiation & Cell State ⓘ

CD133↓, 1,   CD44↓, 1,   CSCs↓, 1,   EMT↓, 1,   STAT3↓, 1,  

Migration ⓘ

E-cadherin↑, 1,   MMP2↓, 1,   N-cadherin↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   Vim↓, 1,   ZO-1↑, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

EGFR↓, 1,  

Immune & Inflammatory Signaling ⓘ

NF-kB↓, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 1,  
Total Targets: 16

Pathway results for Effect on Normal Cells:


Total Targets: 0

Scientific Paper Hit Count for: ZO-1, Zonula occludens-1
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#:674  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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