Fisetin / mTORC2 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


mTORC2, mammalian target of rapamycin (mTOR) complex 2: Click to Expand ⟱
Source:
Type:
mTORC2 associates closely with the plasma membrane, and has been detected in association with ribosomal membranes (11), where it can interact with its key substrates, the AGC kinases including AKT1-3, serum glucose kinase (SGK) isoforms, and protein kinase C (PKC) family members.
Rapamycin is a known allosteric inhibitor of mTORC1, while TOR kinase inhibitors (TOR-KIs) inhibit the activities of both complexes.
AKT, a key substrate of mTORC2, is among the most commonly hyper-activated proteins in cancer. AKT integrates signals from PI3K/mTORC2 and from PI3K/PDK1 to promote cell growth and survival.
Scientific Papers found: Click to Expand⟱
2827- FIS,    The Potential Role of Fisetin, a Flavonoid in Cancer Prevention and Treatment
- Review, Var, NA
*antiOx↑, *Inflam↓, neuroP↑, hepatoP↑, RenoP↑, cycD1/CCND1↓, TumCCA↑, MMPs↓, VEGF↓, MAPK↓, NF-kB↓, angioG↓, Beclin-1↑, LC3s↑, ATG5↑, Bcl-2↓, BAX↑, Casp↑, TNF-α↓, Half-Life↓, MMP↓, mt-ROS↑, cl‑PARP↑, CDK2↓, CDK4↓, Cyt‑c↑, Diablo↑, DR5↑, Fas↑, PCNA↓, Ki-67↓, p‑H3↓, chemoP↑, Ca+2↑, Dose↝, CDC25↓, CDC2↓, CHK1↑, Chk2↑, ATM↑, PCK1↓, RAS↓, p‑p38↓, Rho↓, uPA↓, MMP7↓, MMP13↓, GSK‐3β↑, E-cadherin↑, survivin↓, VEGFR2↓, IAP2↓, STAT3↓, JAK1↓, mTORC1↓, mTORC2↓, NRF2↑,
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↑,
2839- FIS,    Dietary flavonoid fisetin for cancer prevention and treatment
- Review, Var, NA
DNAdam↑, ROS↑, Apoptosis↑, Bcl-2↓, BAX↑, cl‑Casp9↑, cl‑Casp3↑, Cyt‑c↑, lipid-P↓, TumCG↓, TumCA↓, TumCMig↓, TumCI↓, uPA↓, ERK↓, MMP9↓, NF-kB↓, cFos↓, cJun↓, AP-1↓, TumCCA↑, AR↓, mTORC1↓, mTORC2↓, TSC2↑, EGF↓, TGF-β↓, EMT↓, P-gp↓, PI3K↓, Akt↓, mTOR↓, eff↑, ROS↓, ER Stress↑, IRE1↑, ATF4↑, GRP78/BiP↑, ChemoSen↑, CDK2↓, CDK4↓, cycE/CCNE↓, cycD1/CCND1↓, P21↑, COX2↓, Wnt↓, EGFR↓, β-catenin/ZEB1↓, TCF-4↓, MMP7↓, RadioS↑, eff↑,

Showing Research Papers: 1 to 3 of 3

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


Redox & Oxidative Stress ⓘ

lipid-P↓, 1,   NRF2↑, 1,   ROS↓, 2,   ROS↑, 2,   mt-ROS↑, 1,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   CDC2↓, 1,   CDC25↓, 2,   EGF↓, 1,   MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

cMyc↓, 1,   PCK1↓, 1,  

Cell Death ⓘ

Akt↓, 2,   Apoptosis↑, 1,   BAX↑, 3,   Bcl-2↓, 3,   Casp↑, 1,   Casp3↑, 1,   cl‑Casp3↑, 1,   Casp8↑, 1,   cl‑Casp9↑, 2,   Chk2↑, 1,   Cyt‑c↑, 3,   Diablo↑, 1,   DR4↑, 1,   DR5↑, 2,   Fas↑, 1,   IAP2↓, 1,   MAPK↓, 2,   p‑p38↓, 1,   survivin↓, 1,  

Kinase & Signal Transduction ⓘ

HER2/EBBR2↓, 1,   TSC2↑, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 1,   p‑H3↓, 1,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   ER Stress↑, 1,   GRP78/BiP↑, 1,   IRE1↑, 1,  

Autophagy & Lysosomes ⓘ

ATG5↑, 1,   Beclin-1↑, 1,   LC3s↑, 1,  

DNA Damage & Repair ⓘ

ATM↑, 1,   CHK1↑, 1,   DNAdam↑, 1,   P53↑, 1,   cl‑PARP↑, 2,   PCNA↓, 2,  

Cell Cycle & Senescence ⓘ

CDK1↓, 1,   CDK2↓, 3,   CDK4↓, 3,   cycA1/CCNA1↓, 1,   cycD1/CCND1↓, 3,   cycE/CCNE↓, 1,   P21↑, 2,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

cFos↓, 1,   EMT↓, 1,   ERK↓, 1,   GSK‐3β↑, 1,   mTOR↓, 2,   mTORC1↓, 3,   mTORC2↓, 3,   PI3K↓, 2,   RAS↓, 1,   STAT3↓, 1,   TCF-4↓, 1,   TumCG↓, 1,   Wnt↓, 2,  

Migration ⓘ

AP-1↓, 1,   Ca+2↑, 2,   E-cadherin↑, 1,   Ki-67↓, 1,   MMP13↓, 1,   MMP2↓, 1,   MMP7↓, 2,   MMP9↓, 2,   MMPs↓, 1,   Rho↓, 1,   TGF-β↓, 1,   TumCA↓, 1,   TumCI↓, 1,   TumCMig↓, 1,   uPA↓, 3,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   ATF4↑, 1,   EGFR↓, 2,   VEGF↓, 1,   VEGFR2↓, 1,  

Barriers & Transport ⓘ

P-gp↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   JAK1↓, 1,   NF-kB↓, 3,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

AR↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 1,   Dose↑, 1,   Dose↝, 1,   eff↑, 2,   Half-Life↓, 1,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

AR↓, 1,   EGFR↓, 2,   HER2/EBBR2↓, 1,   Ki-67↓, 1,  

Functional Outcomes ⓘ

cardioP↑, 1,   chemoP↑, 1,   hepatoP↑, 1,   neuroP↑, 1,   RenoP↑, 2,  
Total Targets: 111

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 2,  

DNA Damage & Repair ⓘ

p16↓, 1,   P53↓, 1,  

Cell Cycle & Senescence ⓘ

P21↓, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 2,  

Functional Outcomes ⓘ

neuroP↑, 1,  
Total Targets: 6

Scientific Paper Hit Count for: mTORC2, mammalian target of rapamycin (mTOR) complex 2
3 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#:441  State#:%  Dir#:1
  wNotes=0  sortOrder:rid,rpid

 

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