Fisetin / CDK6 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


CDK6, Cyclin-dependent kinase 6: Click to Expand ⟱
Source:
Type:
Cyclin-dependent kinase 6 (CDK6) is another important regulator of the cell cycle, particularly involved in the transition from the G1 phase to the S phase.
CDK6 is frequently overexpressed in various cancers, and its expression levels can serve as a prognostic marker. Targeting CDK6 with specific inhibitors, such as palbociclib (which also targets CDK4), has shown promise in clinical settings, particularly in hormone receptor-positive breast cancer.


Scientific Papers found: Click to Expand⟱
2825- FIS,    Exploring the molecular targets of dietary flavonoid fisetin in cancer
- Review, Var, NA
*Inflam↓, *antiOx↓, *ERK↑, *p‑cMyc↑, *NRF2↑, *GSH↑, *HO-1↑, mTOR↓, PI3K↓, Akt↓, TumCCA↑, cycD1/CCND1↓, cycE/CCNE↓, CDK2↓, CDK4↓, CDK6↓, P21↑, p27↑, JNK↑, MMP2↓, MMP9↓, uPA↓, NF-kB↓, cFos↓, cJun↓, E-cadherin↑, Vim↓, N-cadherin↓, EMT↓, MMP↓, Cyt‑c↑, Diablo↑, Casp↑, cl‑PARP↑, P53↑, COX2↓, PGE2↓, HSP70/HSPA5↓, HSP27↓, DNAdam↑, Casp3↑, Casp9↑, ROS↑, AMPK↑, NO↑, Ca+2↑, mTORC1↓, p70S6↓, ROS↓, ER Stress↑, IRE1↑, ATF4↑, GRP78/BiP↑, eff↑, eff↑, eff↑, RadioS↑, ChemoSen↑, Half-Life↝,
2832- FIS,    Fisetin's Promising Antitumor Effects: Uncovering Mechanisms and Targeting for Future Therapies
- Review, Var, NA
MMP↓, mtDam↑, Cyt‑c↑, Diablo↑, Casp↑, cl‑PARP↑, Bak↑, BIM↑, Bcl-xL↓, Bcl-2↓, P53↑, ROS↑, AMPK↑, Casp9↑, Casp3↑, BID↑, AIF↑, Akt↓, mTOR↓, MAPK↓, Wnt↓, β-catenin/ZEB1↓, TumCCA↑, P21↑, p27↑, cycD1/CCND1↓, cycE/CCNE↓, CDK2↓, CDK4↓, CDK6↓, TumMeta↓, uPA↓, E-cadherin↑, Vim↓, EMT↓, Twist↓, DNAdam↑, ROS↓, COX2↓, PGE2↓, HSF1↓, cFos↓, cJun↓, AP-1↓, Mcl-1↓, NF-kB↓, IRE1↑, ER Stress↑, ATF4↑, GRP78/BiP↑, MMP2↓, MMP9↓, TCF-4↓, MMP7↓, RadioS↑, TOP1↓, TOP2↓,
2843- FIS,    Fisetin and Quercetin: Promising Flavonoids with Chemopreventive Potential
- Review, Var, NA
NRF2↑, Keap1↓, ChemoSen↑, BioAv↓, Cyt‑c↑, Casp3↑, Casp9↑, BAX↑, tumCV↓, Mcl-1↓, cl‑PARP↑, IGF-1↓, Akt↓, CDK6↓, TumCCA↑, P53?, cycD1/CCND1↓, cycE/CCNE↓, CDK2↓, CDK4↓, CDK6↓, MMP2↓, MMP9↓, MMP1↓, MMP7↓, MMP3↓, VEGF↓, PI3K↓, mTOR↓, COX2↓, Wnt↓, EGFR↓, NF-kB↓, ERK↓, ROS↑, angioG↓, TNF-α↓, PGE2↓, iNOS↓, NO↓, IL6↓, HSP70/HSPA5↝, HSP27↝,

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 ⓘ

Keap1↓, 1,   NRF2↑, 1,   ROS↓, 2,   ROS↑, 3,  

Mitochondria & Bioenergetics ⓘ

AIF↑, 1,   MMP↓, 2,   mtDam↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 2,  

Cell Death ⓘ

Akt↓, 3,   Bak↑, 1,   BAX↑, 1,   Bcl-2↓, 1,   Bcl-xL↓, 1,   BID↑, 1,   BIM↑, 1,   Casp↑, 2,   Casp3↑, 3,   Casp9↑, 3,   Cyt‑c↑, 3,   Diablo↑, 2,   iNOS↓, 1,   JNK↑, 1,   MAPK↓, 1,   Mcl-1↓, 2,   p27↑, 2,  

Kinase & Signal Transduction ⓘ

p70S6↓, 1,  

Transcription & Epigenetics ⓘ

cJun↓, 2,   tumCV↓, 1,  

Protein Folding & ER Stress ⓘ

ER Stress↑, 2,   GRP78/BiP↑, 2,   HSF1↓, 1,   HSP27↓, 1,   HSP27↝, 1,   HSP70/HSPA5↓, 1,   HSP70/HSPA5↝, 1,   IRE1↑, 2,  

DNA Damage & Repair ⓘ

DNAdam↑, 2,   P53?, 1,   P53↑, 2,   cl‑PARP↑, 3,  

Cell Cycle & Senescence ⓘ

CDK2↓, 3,   CDK4↓, 3,   cycD1/CCND1↓, 3,   cycE/CCNE↓, 3,   P21↑, 2,   TumCCA↑, 3,  

Proliferation, Differentiation & Cell State ⓘ

cFos↓, 2,   EMT↓, 2,   ERK↓, 1,   IGF-1↓, 1,   mTOR↓, 3,   mTORC1↓, 1,   PI3K↓, 2,   TCF-4↓, 1,   TOP1↓, 1,   TOP2↓, 1,   Wnt↓, 2,  

Migration ⓘ

AP-1↓, 1,   Ca+2↑, 1,   E-cadherin↑, 2,   MMP1↓, 1,   MMP2↓, 3,   MMP3↓, 1,   MMP7↓, 2,   MMP9↓, 3,   N-cadherin↓, 1,   TumMeta↓, 1,   Twist↓, 1,   uPA↓, 2,   Vim↓, 2,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

angioG↓, 1,   ATF4↑, 2,   EGFR↓, 1,   NO↓, 1,   NO↑, 1,   VEGF↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 3,   IL6↓, 1,   NF-kB↓, 3,   PGE2↓, 3,   TNF-α↓, 1,  

Hormonal & Nuclear Receptors ⓘ

CDK6↓, 4,  

Drug Metabolism & Resistance ⓘ

BioAv↓, 1,   ChemoSen↑, 2,   eff↑, 3,   Half-Life↝, 1,   RadioS↑, 2,  

Clinical Biomarkers ⓘ

EGFR↓, 1,   IL6↓, 1,  
Total Targets: 90

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↓, 1,   GSH↑, 1,   HO-1↑, 1,   NRF2↑, 1,  

Core Metabolism/Glycolysis ⓘ

p‑cMyc↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 1,  

Immune & Inflammatory Signaling ⓘ

Inflam↓, 1,  
Total Targets: 7

Scientific Paper Hit Count for: CDK6, Cyclin-dependent kinase 6
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#:895  State#:%  Dir#:%
  wNotes=0  sortOrder:rid,rpid

 

Home Page