Fisetin / GSTs 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


GSTs, Glutathione S-transferases: Click to Expand ⟱
Source:
Type:
Glutathione S-transferases (GSTs) are a family of phase II detoxification enzymes that play key roles in catalyzing the conjugation of glutathione (GSH) to a wide range of electrophilic compounds. This family includes multiple isoenzymes (e.g., GST-α, GST-μ, GST-π) with tissue-specific expression patterns and overlapping as well as distinct substrate specificities.

-GSTs are important for detoxifying potentially harmful compounds, including products of oxidative stress, environmental toxins, and chemotherapeutic agents.
-They contribute to the cellular defense mechanism against oxidative damage and help maintain cellular redox balance.
-Beyond detoxification, GSTs can modulate cell signaling pathways, potentially affecting cell proliferation, apoptosis, and drug resistance.

-GST-π is commonly upregulated in several cancers such as breast, lung, colorectal, and hematologic malignancies.
-Elevated expression of specific GST isoenzymes—most notably GST-π—has been associated with a poorer prognosis in several cancer types. This is often linked to resistance to chemo- or radiotherapy, as higher GST activity can lead to more efficient detoxification of these agents, reducing their cytotoxic effects.
-In contrast, reduced GST expression in some contexts might indicate a less robust detoxification system, which can correlate with increased sensitivity to oxidative stress and possibly a less aggressive tumor phenotype.
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↑,
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↓,
2861- FIS,    The neuroprotective effects of fisetin, a natural flavonoid in neurodegenerative diseases: Focus on the role of oxidative stress
- Review, Nor, NA - Review, Stroke, NA - Review, Park, NA
*antiOx↑, *ROS↓, *neuroP↑, *NO↑, BioAv↝, *BBB↑, *toxicity↑, *eff↑, *GSH↑, *SOD↑, *Aβ↓, *12LOX↓, *COX2↓, *Catalase↑, *Inflam↓, *TNF-α↓, *IL6↑, *lipid-P↓, NF-kB↓, IL1β↓, NRF2↑, HO-1↑, GSTs↑, cognitive↑, *BDNF↑,
2862- FIS,    Fisetin averts oxidative stress in pancreatic tissues of streptozotocin-induced diabetic rat
- in-vivo, Diabetic, NA
*BG↓, *NF-kB↓, *IL1β↓, *NO↓, *Insulin↑, *SOD↑, *Catalase↑, *GPx↑, *GSTs↑,

Showing Research Papers: 1 to 5 of 5

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 5

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

GSTs↓, 2,   GSTs↑, 1,   GSTs↝, 1,   HO-1↑, 2,   NRF2↓, 2,   NRF2↑, 1,   ROS↑, 2,  

Mitochondria & Bioenergetics ⓘ

EGF↓, 1,   MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

ACC↑, 1,   AMPK↑, 1,  

Cell Death ⓘ

Akt↓, 1,   BAD↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   BIM↑, 1,   Casp3↑, 2,   Casp7↑, 1,   Casp8↑, 1,   Cyt‑c↑, 2,   Diablo↑, 1,   DR5↑, 1,   Fas↑, 1,   Mcl-1↓, 1,   MDM2↓, 1,   Myc↓, 1,   p38↓, 1,   TRAIL↑, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 1,   other↝, 1,  

Protein Folding & ER Stress ⓘ

HSP27↓, 1,   HSP70/HSPA5↓, 1,  

DNA Damage & Repair ⓘ

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

Cell Cycle & Senescence ⓘ

CDK2↓, 2,   CDK4↓, 2,   cycA1/CCNA1↓, 1,   cycD1/CCND1↓, 1,   cycE/CCNE↓, 1,   P21↑, 3,   p‑RB1↓, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

cFos↓, 1,   EMT↓, 1,   mTOR↓, 1,   PI3K↓, 1,   TumCG↓, 1,   Wnt↓, 3,  

Migration ⓘ

E-cadherin↑, 1,   Fibronectin↓, 1,   MET↓, 1,   MMP1↓, 1,   MMP2↓, 1,   MMP3↓, 1,   MMP7↓, 1,   MMP9↓, 1,   N-cadherin↓, 1,   Snail↓, 1,   TumMeta↓, 1,   Twist↓, 1,   uPA↓, 1,   Vim↓, 1,   Zeb1↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   ATF4↓, 1,   EGFR↓, 3,   eNOS↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   IL1β↓, 1,   Inflam↓, 1,   NF-kB↓, 4,   p65↓, 1,   PGE2↓, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↝, 1,   ChemoSen↑, 2,   eff↑, 1,   P450↓, 1,   P450↝, 1,   RadioS↑, 1,   selectivity↑, 1,  

Clinical Biomarkers ⓘ

EGFR↓, 3,   Myc↓, 1,  

Functional Outcomes ⓘ

cognitive↑, 1,   Risk↓, 1,  
Total Targets: 87

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,   Catalase↑, 2,   GPx↑, 1,   GSH↑, 1,   GSTs↑, 1,   lipid-P↓, 1,   NRF2↑, 1,   ROS↓, 1,   SOD↑, 2,  

Mitochondria & Bioenergetics ⓘ

Insulin↑, 1,  

Core Metabolism/Glycolysis ⓘ

12LOX↓, 1,  

Angiogenesis & Vasculature ⓘ

NO↓, 1,   NO↑, 1,  

Barriers & Transport ⓘ

BBB↑, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   IL1β↓, 1,   IL6↑, 1,   Inflam↓, 1,   NF-kB↓, 1,   TNF-α↓, 1,  

Synaptic & Neurotransmission ⓘ

BDNF↑, 1,  

Protein Aggregation ⓘ

Aβ↓, 1,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  

Clinical Biomarkers ⓘ

BG↓, 1,   IL6↑, 1,  

Functional Outcomes ⓘ

neuroP↑, 2,   toxicity↑, 1,  
Total Targets: 27

Scientific Paper Hit Count for: GSTs, Glutathione S-transferases
5 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#:1153  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

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