Fisetin / ACC 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


ACC, Acetyl-CoA Carboxylase: Click to Expand ⟱
Source:
Type: enzyme
ACC-α (Acetyl-CoA Carboxylase alpha) is a cytosolic isoform of ACC that is primarily involved in the regulation of fatty acid synthesis in lipogenic tissues, such as liver and adipose tissue. ACC-α is a key enzyme in the biosynthesis of fatty acids, particularly in the context of de novo lipogenesis.
ACC is a biotin-containing enzyme that exists in two main isoforms: ACC-α and ACC-β.
Overexpression of ACC-α has been linked to increased fatty acid synthesis, which can contribute to cancer cell growth and survival.
ACC-β (Acetyl-CoA Carboxylase beta) is a mitochondrial isoform of ACC that is primarily involved in the regulation of fatty acid oxidation.
In general, high ACC expression is associated with:
- Poor prognosis
- Increased tumor size
- Metastasis
- Resistance to chemotherapy
-Poor response to treatment
Low ACC expression is associated with:
- Better prognosis
- Smaller tumor size
- Less metastasis
- Better response to chemotherapy
- Better response to treatment
Scientific Papers found: Click to Expand⟱
2849- FIS,    Activation of reactive oxygen species/AMP activated protein kinase signaling mediates fisetin-induced apoptosis in multiple myeloma U266 cells
- in-vitro, Melanoma, U266
TumCD↑, TumCCA↑, Casp3↑, Bcl-2↓, Mcl-1↓, BAX↑, BIM↑, BAD↑, AMPK↑, ACC↑, p‑Akt↓, p‑mTOR↓, ROS↑, eff↓,
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↓,
2857- FIS,    A review on the chemotherapeutic potential of fisetin: In vitro evidences
- Review, Var, NA
COX2↓, PGE2↓, EGFR↓, Wnt↓, β-catenin/ZEB1↓, TCF↑, Apoptosis↑, Casp3↑, cl‑PARP↑, Bcl-2↓, Mcl-1↓, BAX↑, BIM↑, BAD↑, Akt↓, mTOR↓, ACC↑, Cyt‑c↑, Diablo↑, cl‑Casp8↑, Fas↑, DR5↑, TRAIL↑, Securin↓, CDC2↓, CDC25↓, HSP70/HSPA5↓, CDK2↓, CDK4↓, cycD1/CCND1↓, MMP2↓, uPA↓, NF-kB↓, cFos↓, cJun↓, MEK↓, p‑ERK↓, N-cadherin↓, Vim↓, Snail↓, Fibronectin↓, E-cadherin↓, NF-kB↑, ROS↑, DNAdam↑, MMP↓, CHOP↑, eff↑, ChemoSen↑,

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 ⓘ

GSTs↓, 1,   HO-1↑, 1,   NRF2↓, 1,   ROS↑, 3,  

Mitochondria & Bioenergetics ⓘ

CDC2↓, 1,   CDC25↓, 1,   EGF↓, 1,   MEK↓, 1,   MMP↓, 2,  

Core Metabolism/Glycolysis ⓘ

ACC↑, 3,   AMPK↑, 2,  

Cell Death ⓘ

Akt↓, 2,   p‑Akt↓, 1,   Apoptosis↑, 1,   BAD↑, 3,   BAX↑, 3,   Bcl-2↓, 3,   BIM↑, 3,   Casp3↑, 3,   cl‑Casp8↑, 1,   Cyt‑c↑, 2,   Diablo↑, 2,   DR5↑, 1,   Fas↑, 1,   Mcl-1↓, 3,   Myc↓, 1,   p38↓, 1,   TRAIL↑, 1,   TumCD↑, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 2,  

Protein Folding & ER Stress ⓘ

CHOP↑, 1,   HSP27↓, 1,   HSP70/HSPA5↓, 2,  

DNA Damage & Repair ⓘ

DNAdam↑, 2,   P53↑, 1,   cl‑PARP↑, 2,  

Cell Cycle & Senescence ⓘ

CDK2↓, 2,   CDK4↓, 2,   cycA1/CCNA1↓, 1,   cycD1/CCND1↓, 2,   P21↑, 1,   Securin↓, 1,   TumCCA↑, 2,  

Proliferation, Differentiation & Cell State ⓘ

cFos↓, 2,   EMT↓, 1,   p‑ERK↓, 1,   mTOR↓, 2,   p‑mTOR↓, 1,   PI3K↓, 1,   TCF↑, 1,   Wnt↓, 2,  

Migration ⓘ

E-cadherin↓, 1,   E-cadherin↑, 1,   Fibronectin↓, 2,   MET↓, 1,   MMP1↓, 1,   MMP2↓, 2,   MMP3↓, 1,   MMP7↓, 1,   MMP9↓, 1,   N-cadherin↓, 2,   Snail↓, 2,   TumMeta↓, 1,   Twist↓, 1,   uPA↓, 2,   Vim↓, 2,   Zeb1↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   ATF4↓, 1,   EGFR↓, 2,   eNOS↓, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 2,   NF-kB↓, 2,   NF-kB↑, 1,   p65↓, 1,   PGE2↓, 1,  

Drug Metabolism & Resistance ⓘ

ChemoSen↑, 2,   eff↓, 1,   eff↑, 2,  

Clinical Biomarkers ⓘ

EGFR↓, 2,   Myc↓, 1,  
Total Targets: 83

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 1,   NRF2↑, 1,  

Functional Outcomes ⓘ

neuroP↑, 1,  
Total Targets: 3

Scientific Paper Hit Count for: ACC, Acetyl-CoA Carboxylase
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#:932  State#:%  Dir#:2
  wNotes=0  sortOrder:rid,rpid

 

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